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Brief Report
Genetics
Clinical Characteristics of Diabetes in People with Mitochondrial DNA 3243A>G Mutation in Korea
Eun Hoo Rho, Sang Ik Baek, Heerah Lee, Moon-Woo Seong, Jong-Hee Chae, Kyong Soo Park, Soo Heon Kwak
Received March 10, 2023  Accepted July 20, 2023  Published online February 1, 2024  
DOI: https://doi.org/10.4093/dmj.2023.0078    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Maternally inherited diabetes and deafness (MIDD) is a rare mitochondrial disorder primarily resulting from m.3243A>G mutation. The clinical characteristics of MIDD exhibit significant heterogeneity. Our study aims to delineate these characteristics and determine the potential correlation with m.3243A>G heteroplasmy levels. This retrospective, descriptive study encompassed patients with confirmed m.3243A>G mutation and diabetes mellitus at Seoul National University Hospital. Our cohort comprises 40 patients with MIDD, with a mean age at study enrollment of 33.3±12.9 years and an average % of heteroplasmy of 30.0%± 14.6% in the peripheral blood. The most prevalent comorbidity was hearing loss (90%), followed by albuminuria (61%), seizure (38%), and stroke (33%). We observed a significant negative correlation between % of heteroplasmy and age at diabetes diagnosis. These clinical features can aid in the suspicion of MIDD and further consideration of genetic testing for m.3243A>G mutation.
Reviews
Basic Research
Mitochondrial Stress and Mitokines: Therapeutic Perspectives for the Treatment of Metabolic Diseases
Benyuan Zhang, Joon Young Chang, Min Hee Lee, Sang-Hyeon Ju, Hyon-Seung Yi, Minho Shong
Diabetes Metab J. 2024;48(1):1-18.   Published online January 3, 2024
DOI: https://doi.org/10.4093/dmj.2023.0115
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AbstractAbstract PDFPubReader   ePub   
Mitochondrial stress and the dysregulated mitochondrial unfolded protein response (UPRmt) are linked to various diseases, including metabolic disorders, neurodegenerative diseases, and cancer. Mitokines, signaling molecules released by mitochondrial stress response and UPRmt, are crucial mediators of inter-organ communication and influence systemic metabolic and physiological processes. In this review, we provide a comprehensive overview of mitokines, including their regulation by exercise and lifestyle interventions and their implications for various diseases. The endocrine actions of mitokines related to mitochondrial stress and adaptations are highlighted, specifically the broad functions of fibroblast growth factor 21 and growth differentiation factor 15, as well as their specific actions in regulating inter-tissue communication and metabolic homeostasis. Finally, we discuss the potential of physiological and genetic interventions to reduce the hazards associated with dysregulated mitokine signaling and preserve an equilibrium in mitochondrial stress-induced responses. This review provides valuable insights into the mechanisms underlying mitochondrial regulation of health and disease by exploring mitokine interactions and their regulation, which will facilitate the development of targeted therapies and personalized interventions to improve health outcomes and quality of life.
Basic Research
Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases
Byung Soo Kong, Changhan Lee, Young Min Cho
Diabetes Metab J. 2023;47(3):315-324.   Published online February 24, 2023
DOI: https://doi.org/10.4093/dmj.2022.0333
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  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDFPubReader   ePub   
Mitochondria are complex metabolic organelles with manifold pathophysiological implications in diabetes. Currently published mitochondrial-encoded peptides, which are expressed from the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), 16S rRNA (humanin and short humanin like peptide 1-6 [SHLP1-6]), or small human mitochondrial open reading frame over serine tRNA (SHMOOSE) are associated with regulation of cellular metabolism and insulin action in age-related diseases, such as type 2 diabetes mellitus. This review focuses mainly on recent advances in MOTS-c research with regards to diabetes, including both type 1 and type 2. The emerging understanding of MOTS-c in diabetes may provide insight into the development of new therapies for diabetes and other age or senescence-related diseases.

Citations

Citations to this article as recorded by  
  • Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives
    Satadeepa Kal, Sumana Mahata, Suborno Jati, Sushil K. Mahata
    Peptides.2024; 172: 171147.     CrossRef
  • Mitochondrial Stress and Mitokines: Therapeutic Perspectives for the Treatment of Metabolic Diseases
    Benyuan Zhang, Joon Young Chang, Min Hee Lee, Sang-Hyeon Ju, Hyon-Seung Yi, Minho Shong
    Diabetes & Metabolism Journal.2024; 48(1): 1.     CrossRef
  • Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes
    Alejandra María Rivera Nieves, Brian Michael Wauford, Accalia Fu
    Frontiers in Molecular Biosciences.2024;[Epub]     CrossRef
Basic Research
The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4
Min-Ji Kim, Ibotombi Singh Sinam, Zerwa Siddique, Jae-Han Jeon, In-Kyu Lee
Diabetes Metab J. 2023;47(2):153-163.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2022.0305
  • 4,790 View
  • 363 Download
  • 5 Web of Science
  • 6 Crossref
AbstractAbstract PDFPubReader   ePub   
Sarcopenia, defined as a progressive loss of muscle mass and function, is typified by mitochondrial dysfunction and loss of mitochondrial resilience. Sarcopenia is associated not only with aging, but also with various metabolic diseases characterized by mitochondrial dyshomeostasis. Pyruvate dehydrogenase kinases (PDKs) are mitochondrial enzymes that inhibit the pyruvate dehydrogenase complex, which controls pyruvate entry into the tricarboxylic acid cycle and the subsequent adenosine triphosphate production required for normal cellular activities. PDK4 is upregulated in mitochondrial dysfunction-related metabolic diseases, especially pathologic muscle conditions associated with enhanced muscle proteolysis and aberrant myogenesis. Increases in PDK4 are associated with perturbation of mitochondria-associated membranes and mitochondrial quality control, which are emerging as a central mechanism in the pathogenesis of metabolic disease-associated muscle atrophy. Here, we review how mitochondrial dysfunction affects sarcopenia, focusing on the role of PDK4 in mitochondrial homeostasis. We discuss the molecular mechanisms underlying the effects of PDK4 on mitochondrial dysfunction in sarcopenia and show that targeting mitochondria could be a therapeutic target for treating sarcopenia.

Citations

Citations to this article as recorded by  
  • Synthesis, activatory effects, molecular docking and ADME studies as rabbit muscle pyruvate kinase activators of ureido phenyl substituted 1,4-dihydropyridine derivatives
    Mustafa Oğuzhan Kaya, Tuna Demirci, Ümit Çalışır, Oğuzhan Özdemir, Yeşim Kaya, Mustafa Arslan
    Research on Chemical Intermediates.2024; 50(1): 437.     CrossRef
  • Unraveling the causes of sarcopenia: Roles of neuromuscular junction impairment and mitochondrial dysfunction
    Yanmei Miao, Leiyu Xie, Jiamei Song, Xing Cai, Jinghe Yang, Xinglong Ma, Shaolin Chen, Peng Xie
    Physiological Reports.2024;[Epub]     CrossRef
  • Metabolic clues to aging: exploring the role of circulating metabolites in frailty, sarcopenia and vascular aging related traits and diseases
    Zonghao Qian, Yuzhen Huang, Yucong Zhang, Ni Yang, Ziwei Fang, Cuntai Zhang, Le Zhang
    Frontiers in Genetics.2024;[Epub]     CrossRef
  • Inhibition of Pyruvate Dehydrogenase Kinase 4 Protects Cardiomyocytes from lipopolysaccharide-Induced Mitochondrial Damage by Reducing Lactate Accumulation
    Tangtian Chen, Qiumin Xie, Bin Tan, Qin Yi, Han Xiang, Rui Wang, Qin Zhou, Bolin He, Jie Tian, Jing Zhu, Hao Xu
    Inflammation.2024;[Epub]     CrossRef
  • Effect of resistance training plus enriched probiotic supplement on sestrin2, oxidative stress, and mitophagy markers in elderly male Wistar rats
    Majid Mohabbat, Hamid Arazi
    Scientific Reports.2024;[Epub]     CrossRef
  • Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases
    Yue Zhang, Meiyan Sun, Hongxiang Zhao, Zhengyan Wang, Yanan Shi, Jianxin Dong, Kaifang Wang, Xi Wang, Xingyue Li, Haiyan Qi, Xiaoyong Zhao
    International Journal of Nanomedicine.2023; Volume 18: 7559.     CrossRef
Sulwon Lecture 2021
Basic Research
Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c)
Tae Kwan Yoon, Chan Hee Lee, Obin Kwon, Min-Seon Kim
Diabetes Metab J. 2022;46(3):402-413.   Published online May 25, 2022
DOI: https://doi.org/10.4093/dmj.2022.0092
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  • 238 Download
  • 8 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   ePub   
Low levels of mitochondrial stress are beneficial for organismal health and survival through a process known as mitohormesis. Mitohormetic responses occur during or after exercise and may mediate some salutary effects of exercise on metabolism. Exercise-related mitohormesis involves reactive oxygen species production, mitochondrial unfolded protein response (UPRmt), and release of mitochondria-derived peptides (MDPs). MDPs are a group of small peptides encoded by mitochondrial DNA with beneficial metabolic effects. Among MDPs, mitochondrial ORF of the 12S rRNA type-c (MOTS-c) is the most associated with exercise. MOTS-c expression levels increase in skeletal muscles, systemic circulation, and the hypothalamus upon exercise. Systemic MOTS-c administration increases exercise performance by boosting skeletal muscle stress responses and by enhancing metabolic adaptation to exercise. Exogenous MOTS-c also stimulates thermogenesis in subcutaneous white adipose tissues, thereby enhancing energy expenditure and contributing to the anti-obesity effects of exercise training. This review briefly summarizes the mitohormetic mechanisms of exercise with an emphasis on MOTS-c.

Citations

Citations to this article as recorded by  
  • Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives
    Satadeepa Kal, Sumana Mahata, Suborno Jati, Sushil K. Mahata
    Peptides.2024; 172: 171147.     CrossRef
  • Beneficial Effects of Low-Grade Mitochondrial Stress on Metabolic Diseases and Aging
    Se Hee Min, Gil Myoung Kang, Jae Woo Park, Min-Seon Kim
    Yonsei Medical Journal.2024; 65(2): 55.     CrossRef
  • Roles of Myokines and Muscle-Derived Extracellular Vesicles in Musculoskeletal Deterioration under Disuse Conditions
    Jie Zhang, Yunfang Gao, Jiangwei Yan
    Metabolites.2024; 14(2): 88.     CrossRef
  • Antifragility and antiinflammaging: Can they play a role for a healthy longevity?
    Fabiola Olivieri, Francesco Prattichizzo, Fabrizia Lattanzio, Anna Rita Bonfigli, Liana Spazzafumo
    Ageing Research Reviews.2023; 84: 101836.     CrossRef
  • MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation
    Yuejun Zheng, Zilin Wei, Tianhui Wang
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • MOTS-c: A potential anti-pulmonary fibrosis factor derived by mitochondria
    Zewei Zhang, Dongmei Chen, Kaili Du, Yaping Huang, Xingzhe Li, Quwen Li, Xiaoting Lv
    Mitochondrion.2023; 71: 76.     CrossRef
  • Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases
    Byung Soo Kong, Changhan Lee, Young Min Cho
    Diabetes & Metabolism Journal.2023; 47(3): 315.     CrossRef
  • MOTS-c Serum Concentration Positively Correlates with Lower-Body Muscle Strength and Is Not Related to Maximal Oxygen Uptake—A Preliminary Study
    Remigiusz Domin, Michał Pytka, Mikołaj Żołyński, Jan Niziński, Marcin Rucinski, Przemysław Guzik, Jacek Zieliński, Marek Ruchała
    International Journal of Molecular Sciences.2023; 24(19): 14951.     CrossRef
  • Unique Properties of Apicomplexan Mitochondria
    Ian M. Lamb, Ijeoma C. Okoye, Michael W. Mather, Akhil B. Vaidya
    Annual Review of Microbiology.2023; 77(1): 541.     CrossRef
Original Article
Metabolic Risk/Epidemiology
Effect of Low-Dose Persistent Organic Pollutants on Mitochondrial Function: Human and in Vitro Evidence
Se-A Kim, Hoyul Lee, Sung-Mi Park, Mi-Jin Kim, Yu-Mi Lee, Young-Ran Yoon, Hyun-Kyung Lee, Hyo-Bang Moon, In-Kyu Lee, Duk-Hee Lee
Diabetes Metab J. 2022;46(4):592-604.   Published online January 26, 2022
DOI: https://doi.org/10.4093/dmj.2021.0132
  • 5,130 View
  • 237 Download
  • 5 Web of Science
  • 7 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Chronic exposure to low-dose persistent organic pollutants (POPs) can induce mitochondrial dysfunction. This study evaluated the association between serum POP concentrations and oxygen consumption rate (OCR) as a marker of mitochondrial function in humans and in vitro cells.
Methods
Serum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in 323 adults. The OCRs of platelets and peripheral blood mononuclear cells (PBMCs) were assessed in 20 mL of fresh blood using a Seahorse XF analyzer. Additionally, the in vitro effects of Arochlor-1254, β-hexachlorocyclohexane, and p,p´-dichlorodiphenyltrichloroethane at concentrations of 0.1 pM to 100 nM were evaluated in human platelets, human PBMCs, and Jurkat T-cells.
Results
The association between serum POP concentrations and OCR differed depending on the cell type. As serum OCP concentrations increased, basal platelet OCR levels decreased significantly; according to the OCP quintiles of summary measure, they were 8.6, 9.6, 8.2, 8.0, and 7.1 pmol/min/μg (P trend=0.005). Notably, the basal PBMC OCR levels decreased remarkably as the serum PCB concentration increased. PBMC OCR levels were 46.5, 34.3, 29.1, 16.5, and 13.1 pmol/min/μg according to the PCB quintiles of summary measure (P trend <0.001), and this inverse association was consistently observed in all subgroups stratified by age, sex, obesity, type 2 diabetes mellitus, and hypertension, respectively. In vitro experimental studies have also demonstrated that chronic exposure to low-dose POPs could decrease OCR levels.
Conclusion
The findings from human and in vitro studies suggest that chronic exposure to low-dose POPs can induce mitochondrial dysfunction by impairing oxidative phosphorylation.

Citations

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  • Persistent Organic Pollutants released from decomposed adipose tissue affect mitochondrial enzyme function in the brain and eyes other than the liver
    Dongshin Yang, Eun Ko, Hwayeon Lim, Hyojin Lee, Kitae Kim, Moonsung Choi, Sooim Shin
    Environmental Science and Pollution Research.2024; 31(7): 10648.     CrossRef
  • Can lipophilic pollutants in adipose tissue explain weight change‐related risk in type 2 diabetes mellitus?
    Duk‐Hee Lee, In‐Kyu Lee
    Journal of Diabetes Investigation.2023; 14(4): 528.     CrossRef
  • Mitochondrial and metabolic features of salugenesis and the healing cycle
    Robert K. Naviaux
    Mitochondrion.2023; 70: 131.     CrossRef
  • Obesity Paradox in Sepsis: Role of Adipose Tissue in Storing Mitochondrial Toxins
    Duk-Hee Lee
    Critical Care Medicine.2023; 51(8): e172.     CrossRef
  • Human Preadipocytes Differentiated under Hypoxia following PCB126 Exposure during Proliferation: Effects on Differentiation, Glucose Uptake and Adipokine Profile
    Zeinab El Amine, Jean-François Mauger, Pascal Imbeault
    Cells.2023; 12(18): 2326.     CrossRef
  • Is micronucleus assay in oral exfoliated cells a useful biomarker for biomonitoring populations exposed to pesticides? A systematic review with meta-analysis
    Ingra Tais Malacarne, Wilton Mitsunari Takeshita, Daniel Vitor de Souza, Barbara dos Anjos Rosario, Milena de Barros Viana, Ana Claudia Muniz Renno, Daisy Maria Favero Salvadori, Daniel Araki Ribeiro
    Environmental Science and Pollution Research.2022; 29(43): 64392.     CrossRef
  • Comment on: Obesity is Associated with Improved Postoperative Overall Survival, Independent of Skeletal Muscle Mass in Lung Adenocarcinoma by Lee et al.
    Duk‐Hee Lee
    Journal of Cachexia, Sarcopenia and Muscle.2022; 13(5): 2576.     CrossRef
Review
Basic Research
Mitochondrial TFAM as a Signaling Regulator between Cellular Organelles: A Perspective on Metabolic Diseases
Jin-Ho Koh, Yong-Woon Kim, Dae-Yun Seo, Tae-Seo Sohn
Diabetes Metab J. 2021;45(6):853-865.   Published online November 22, 2021
DOI: https://doi.org/10.4093/dmj.2021.0138
  • 6,572 View
  • 274 Download
  • 12 Web of Science
  • 14 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Tissues actively involved in energy metabolism are more likely to face metabolic challenges from bioenergetic substrates and are susceptible to mitochondrial dysfunction, leading to metabolic diseases. The mitochondria receive signals regarding the metabolic states in cells and transmit them to the nucleus or endoplasmic reticulum (ER) using calcium (Ca2+) for appropriate responses. Overflux of Ca2+ in the mitochondria or dysregulation of the signaling to the nucleus and ER could increase the incidence of metabolic diseases including insulin resistance and type 2 diabetes mellitus. Mitochondrial transcription factor A (Tfam) may regulate Ca2+ flux via changing the mitochondrial membrane potential and signals to other organelles such as the nucleus and ER. Since Tfam is involved in metabolic function in the mitochondria, here, we discuss the contribution of Tfam in coordinating mitochondria-ER activities for Ca2+ flux and describe the mechanisms by which Tfam affects mitochondrial Ca2+ flux in response to metabolic challenges.

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  • Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong
    Bingjia Zhao, Qian Zhang, Yiqian He, Weifang Cao, Wei Song, Xiaochun Liang
    Journal of Pharmaceutical Analysis.2024; 14(2): 225.     CrossRef
  • Mitochondrial damage‐associated molecular patterns: A new insight into metabolic inflammation in type 2 diabetes mellitus
    Yan Wang, Jingwu Wang, Si‐Yu Tao, Zhengting Liang, Rong xie, Nan‐nan Liu, Ruxue Deng, Yuelin Zhang, Deqiang Deng, Guangjian Jiang
    Diabetes/Metabolism Research and Reviews.2024;[Epub]     CrossRef
  • Altered Energy Metabolism, Mitochondrial Dysfunction, and Redox Imbalance Influencing Reproductive Performance in Granulosa Cells and Oocyte During Aging
    Hiroshi Kobayashi, Chiharu Yoshimoto, Sho Matsubara, Hiroshi Shigetomi, Shogo Imanaka
    Reproductive Sciences.2024; 31(4): 906.     CrossRef
  • When Our Best Friend Becomes Our Worst Enemy: The Mitochondrion in Trauma, Surgery, and Critical Illness
    May-Kristin Torp, Kåre-Olav Stensløkken, Jarle Vaage
    Journal of Intensive Care Medicine.2024;[Epub]     CrossRef
  • Effects of the anti-inflammatory drug celecoxib on cell death signaling in human colon cancer
    Ryuto Maruyama, Yuki Kiyohara, Yasuhiro Kudo, Tomoyasu Sugiyama
    Naunyn-Schmiedeberg's Archives of Pharmacology.2023; 396(6): 1171.     CrossRef
  • gp130 Activates Mitochondrial Dynamics for Hepatocyte Survival in a Model of Steatohepatitis
    Daria Shunkina, Anastasia Dakhnevich, Egor Shunkin, Olga Khaziakhmatova, Valeria Shupletsova, Maria Vulf, Alexandra Komar, Elena Kirienkova, Larisa Litvinova
    Biomedicines.2023; 11(2): 396.     CrossRef
  • Pharmacological Activation of Rev-erbα Attenuates Doxorubicin-Induced Cardiotoxicity by PGC-1α Signaling Pathway
    Runmei Zou, Shuo Wang, Hong Cai, Yuwen Wang, Cheng Wang, Vivek Pandey
    Cardiovascular Therapeutics.2023; 2023: 1.     CrossRef
  • Protective Effect of Ergothioneine against 7-Ketocholesterol-Induced Mitochondrial Damage in hCMEC/D3 Human Brain Endothelial Cells
    Damien Meng-Kiat Leow, Irwin Kee-Mun Cheah, Zachary Wei-Jie Fong, Barry Halliwell, Wei-Yi Ong
    International Journal of Molecular Sciences.2023; 24(6): 5498.     CrossRef
  • Effect of PPARγ on oxidative stress in diabetes-related dry eye
    Jing Wang, Shuangping Chen, Xiuxiu Zhao, Qian Guo, Ruibo Yang, Chen Zhang, Yue Huang, Lechong Ma, Shaozhen Zhao
    Experimental Eye Research.2023; 231: 109498.     CrossRef
  • Chiisanoside Mediates the Parkin/ZNF746/PGC-1α Axis by Downregulating MiR-181a to Improve Mitochondrial Biogenesis in 6-OHDA-Caused Neurotoxicity Models In Vitro and In Vivo: Suggestions for Prevention of Parkinson’s Disease
    Yu-Ling Hsu, Hui-Jye Chen, Jia-Xin Gao, Ming-Yang Yang, Ru-Huei Fu
    Antioxidants.2023; 12(9): 1782.     CrossRef
  • TBBPA causes apoptosis in grass carp hepatocytes involving destroyed ER-mitochondrial function
    Dongxu Han, Naixi Yang, Huanyi Liu, Yujie Yao, Shiwen Xu
    Chemosphere.2023; 341: 139974.     CrossRef
  • The Protective Mechanism of TFAM on Mitochondrial DNA and its Role in Neurodegenerative Diseases
    Ying Song, Wenjun Wang, Beibei Wang, Qiwen Shi
    Molecular Neurobiology.2023;[Epub]     CrossRef
  • Impact of Roux-en-Y Gastric Bypass on Mitochondrial Biogenesis and Dynamics in Leukocytes of Obese Women
    Zaida Abad-Jiménez, Teresa Vezza, Sandra López-Domènech, Meylin Fernández-Reyes, Francisco Canet, Carlos Morillas, Segundo Ángel Gómez-Abril, Celia Bañuls, Víctor M. Víctor, Milagros Rocha
    Antioxidants.2022; 11(7): 1302.     CrossRef
  • The Effects of Galgunhwanggumhwangryun-tang on Glucose and Energy Metabolism in C2C12 Myotubes
    Jihong Oh, Song-Yi Han, Soo Kyoung Lim, Hojun Kim
    Journal of Korean Medicine for Obesity Research.2022; 22(2): 93.     CrossRef
Original Article
Basic Research
Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell
Kyung-Soo Kim, Yeon Kyung Choi, Mi Jin Kim, Jung Wook Hwang, Kyunghoon Min, Sang Youn Jung, Soo-Kyung Kim, Yong-Soo Choi, Yong-Wook Cho
Diabetes Metab J. 2021;45(2):260-269.   Published online July 10, 2020
DOI: https://doi.org/10.4093/dmj.2019.0191
  • 9,398 View
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  • 8 Web of Science
  • 8 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Umbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell.

Methods

Insulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell.

Results

Glucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance.

Conclusion

UC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

Citations

Citations to this article as recorded by  
  • Neurotransmitters in Type 2 Diabetes and the Control of Systemic and Central Energy Balance
    Amnah Al-Sayyar, Maha M. Hammad, Michayla R. Williams, Mohammed Al-Onaizi, Jehad Abubaker, Fawaz Alzaid
    Metabolites.2023; 13(3): 384.     CrossRef
  • Neuroprotective Effect of Wharton’s Jelly-Derived Mesenchymal Stem Cell-Conditioned Medium (WJMSC-CM) on Diabetes-Associated Cognitive Impairment by Improving Oxidative Stress, Neuroinflammation, and Apoptosis
    Zohre Aghaei, Narges Karbalaei, Mohammad Reza Namavar, Masoud Haghani, Mahboobeh Razmkhah, Mahdi Khorsand Ghaffari, Marzieh Nemati, Andrea Ballini
    Stem Cells International.2023; 2023: 1.     CrossRef
  • Mesenchymal-Stem Cell-Derived Conditioned Media Versus Exosomes in the Treatment of Rat Model of Polycystic Ovary: An Attempt to Understand the Underlying Mechanisms (Biochemical and Histological Study)
    Soha Abd-elkawy Abd-elwahab, Noura Hassan Khamis, Rehab Ahmed Rifaai, Nashwa Fathy Gamal El-Tahawy, Randa Ahmed Ibrahim
    Microscopy and Microanalysis.2023; 29(3): 1244.     CrossRef
  • Therapeutic Potential of Mesenchymal Stem Cell‐Derived Conditioned Medium for Diabetes Mellitus and Related Complications
    Basak Isildar, Serbay Ozkan, Meral Koyuturk
    Advanced Therapeutics.2023;[Epub]     CrossRef
  • Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach
    Priyamvada Amol Arte, Kanchanlata Tungare, Mustansir Bhori, Renitta Jobby, Jyotirmoi Aich
    Human Cell.2023; 37(1): 54.     CrossRef
  • Perinatal Stem Cell Therapy to Treat Type 1 Diabetes Mellitus: A Never-Say-Die Story of Differentiation and Immunomodulation
    Francesca Paris, Valeria Pizzuti, Pasquale Marrazzo, Andrea Pession, Francesco Alviano, Laura Bonsi
    International Journal of Molecular Sciences.2022; 23(23): 14597.     CrossRef
  • Mesenchymal Stem Cell-Derived Apoptotic Bodies: Biological Functions and Therapeutic Potential
    Huixue Tang, Huikun Luo, Zihan Zhang, Di Yang
    Cells.2022; 11(23): 3879.     CrossRef
  • Human umbilical cord mesenchymal stem cells in type 2 diabetes mellitus: the emerging therapeutic approach
    Andreia Gomes, Pedro Coelho, Raquel Soares, Raquel Costa
    Cell and Tissue Research.2021; 385(3): 497.     CrossRef
Sulwon Lecture 2019
Pathophysiology
The Role of Growth Differentiation Factor 15 in Energy Metabolism
Joon Young Chang, Hyun Jung Hong, Seul Gi Kang, Jung Tae Kim, Ben Yuan Zhang, Minho Shong
Diabetes Metab J. 2020;44(3):363-371.   Published online June 29, 2020
DOI: https://doi.org/10.4093/dmj.2020.0087
  • 8,090 View
  • 226 Download
  • 15 Web of Science
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AbstractAbstract PDFPubReader   

Growth differentiation factor 15 (GDF15) is receiving great interest beyond its role as an aging and disease-related biomarker. Recent discovery of its receptor, glial cell line-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL), suggests a central role in appetite regulation. However, there is also considerable evidence that GDF15 may have peripheral activity through an as-of-yet undiscovered mode of action. This raises the question as to whether increased GDF15 induction during pathophysiologic conditions also suppresses appetite. The present review will briefly introduce the discovery of GDF15 and describe the different contexts under which GDF15 is induced, focusing on its induction during mitochondrial dysfunction. We will further discuss the metabolic role of GDF15 under various pathophysiological conditions and conclude with possible therapeutic applications.

Citations

Citations to this article as recorded by  
  • Growth differentiation factor-15 is an IFN-γ regulated mediator of infection-induced weight loss and the hepatic FGF21 response
    Jojo Reyes, Yanlin Zhao, Krushang Pandya, George S. Yap
    Brain, Behavior, and Immunity.2024; 116: 24.     CrossRef
  • Biomarkers of disability worsening in inactive primary progressive multiple sclerosis
    Maria-Elizabeth Baeva, Isabelle Tottenham, Marcus Koch, Carlos Camara-Lemarroy
    Journal of Neuroimmunology.2024; 387: 578268.     CrossRef
  • Tricarboxylic Acid Cycle Intermediates and Individual Ageing
    Natalia Kurhaluk
    Biomolecules.2024; 14(3): 260.     CrossRef
  • A long‐acting GDF15 analog causes robust, sustained weight loss and reduction of food intake in an obese nonhuman primate model
    Songmao Zheng, David Polidori, Yuanping Wang, Brian Geist, Xiefan Lin‐Schmidt, Jennifer L. Furman, Serena Nelson, Andrea R. Nawrocki, Simon A. Hinke
    Clinical and Translational Science.2023; 16(8): 1431.     CrossRef
  • GDF15 enhances body weight and adiposity reduction in obese mice by leveraging the leptin pathway
    Samuel N. Breit, Rakesh Manandhar, Hong-Ping Zhang, Michelle Lee-Ng, David A. Brown, Vicky Wang-Wei Tsai
    Cell Metabolism.2023; 35(8): 1341.     CrossRef
  • Serum growth differentiation factor-15 (GDF-15) is a biomarker of cardiac manifestations in children with COVID-19
    Sally Raafat Ishak, Mona Mostafa El Ganzoury, Eman Mahmoud Fouda, Maha Ahmad Anwar, Amany Moustafa Kamal, Heba Mostafa Hamza, Nehad Ahmed Bakry
    European Journal of Medical Research.2023;[Epub]     CrossRef
  • Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia
    Eunbyul Yeom, Kweon Yu
    Experimental & Molecular Medicine.2022; 54(4): 426.     CrossRef
  • Investigating the combination of plasma amyloid-beta and geroscience biomarkers on the incidence of clinically meaningful cognitive decline in older adults
    Wan-Hsuan Lu, Kelly Virecoulon Giudici, John E. Morley, Sophie Guyonnet, Angelo Parini, Geetika Aggarwal, Andrew D. Nguyen, Yan Li, Randall J. Bateman, Bruno Vellas, Philipe de Souto Barreto, Bruno Vellas, Sophie Guyonnet, Isabelle Carrié, Lauréane Brigit
    GeroScience.2022; 44(3): 1489.     CrossRef
  • The Potential Role of Growth Differentiation Factor 15 in COVID-19: A Corollary Subjective Effect or Not?
    Ahmad O. Babalghith, Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Michel De Waard, Jean-Marc Sabatier, Hebatallah M. Saad, Gaber El-Saber Batiha
    Diagnostics.2022; 12(9): 2051.     CrossRef
  • Metformin and growth differentiation factor 15 (GDF15) in type 2 diabetes mellitus: A hidden treasure
    Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb, Athanasios Alexiou, Marios Papadakis, Eman Hassan Nadwa, Sarah M. Albogami, Mohammed Alorabi, Hebatallah M. Saad, Gaber El‐Saber Batiha
    Journal of Diabetes.2022; 14(12): 806.     CrossRef
  • Effects of Exercise Intervention on Mitochondrial Stress Biomarkers in Metabolic Syndrome Patients: A Randomized Controlled Trial
    Jae Seung Chang, Jun Namkung
    International Journal of Environmental Research and Public Health.2021; 18(5): 2242.     CrossRef
  • Neurological & psychological aspects of Barth syndrome: Clinical manifestations and potential pathogenic mechanisms
    Melissa Olivar-Villanueva, Mindong Ren, Colin K.L. Phoon
    Mitochondrion.2021; 61: 188.     CrossRef
  • The metabolic role of spermidine in obesity: Evidence from cells to community
    Yanee Choksomngam, Sintip Pattanakuhar, Nipon Chattipakorn, Siriporn C. Chattipakorn
    Obesity Research & Clinical Practice.2021; 15(4): 315.     CrossRef
  • The Role of GDF15 as a Myomitokine
    Kornelia Johann, Maximilian Kleinert, Susanne Klaus
    Cells.2021; 10(11): 2990.     CrossRef
Review
Basic Research
Mitochondrial Mechanisms in Diabetic Cardiomyopathy
Johannes Gollmer, Andreas Zirlik, Heiko Bugger
Diabetes Metab J. 2020;44(1):33-53.   Published online February 21, 2020
DOI: https://doi.org/10.4093/dmj.2019.0185
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AbstractAbstract PDFPubReader   

Mitochondrial medicine is increasingly discussed as a promising therapeutic approach, given that mitochondrial defects are thought to contribute to many prevalent diseases and their complications. In individuals with diabetes mellitus (DM), defects in mitochondrial structure and function occur in many organs throughout the body, contributing both to the pathogenesis of DM and complications of DM. Diabetic cardiomyopathy (DbCM) is increasingly recognized as an underlying cause of increased heart failure in DM, and several mitochondrial mechanisms have been proposed to contribute to the development of DbCM. Well established mechanisms include myocardial energy depletion due to impaired adenosine triphosphate (ATP) synthesis and mitochondrial uncoupling, and increased mitochondrial oxidative stress. A variety of upstream mechanisms of impaired ATP regeneration and increased mitochondrial reactive oxygen species have been proposed, and recent studies now also suggest alterations in mitochondrial dynamics and autophagy, impaired mitochondrial Ca2+ uptake, decreased cardiac adiponectin action, increased O-GlcNAcylation, and impaired activity of sirtuins to contribute to mitochondrial defects in DbCM, among others. In the current review, we present and discuss the evidence that underlies both established and recently proposed mechanisms that are thought to contribute to mitochondrial dysfunction in DbCM.

Citations

Citations to this article as recorded by  
  • SIRT1: a promising therapeutic target in type 2 diabetes mellitus
    Ainaz Mihanfar, Maryam Akbarzadeh, Saber Ghazizadeh Darband, Shirin Sadighparvar, Maryam Majidinia
    Archives of Physiology and Biochemistry.2024; 130(1): 13.     CrossRef
  • Effect of exercise on improving myocardial mitochondrial function in decreasing diabetic cardiomyopathy
    Feng Zhang, Jian jian Lin, Hao nan Tian, Jun Wang
    Experimental Physiology.2024; 109(2): 190.     CrossRef
  • Cardioprotective effects of asiaticoside against diabetic cardiomyopathy: Activation of the AMPK/Nrf2 pathway
    Chennian Xu, Lin Xia, Dengyue Xu, Yang Liu, Ping Jin, Mengen Zhai, Yu Mao, Yiwei Wang, Anguo Wen, Jian Yang, Lifang Yang
    Journal of Cellular and Molecular Medicine.2024;[Epub]     CrossRef
  • Ferroptosis: Mechanisms and role in diabetes mellitus and its complications
    Pan Liu, Zhengdong Zhang, Yichen Cai, Zhaoying Li, Qian Zhou, Qiu Chen
    Ageing Research Reviews.2024; 94: 102201.     CrossRef
  • Salidroside Alleviates Myocardial Ischemia Reperfusion by Balancing Mitochondrial Homeostasis via Nrf2
    Tingxu Yan, Xu Li, Xin Wang, Bosai He, Ying Jia, Wei Xiao, Rong He
    Journal of Food Biochemistry.2024; 2024: 1.     CrossRef
  • AGO2 Protects Against Diabetic Cardiomyopathy by Activating Mitochondrial Gene Translation
    Jiabing Zhan, Kunying Jin, Rong Xie, Jiahui Fan, Yuyan Tang, Chen Chen, Huaping Li, Dao Wen Wang
    Circulation.2024; 149(14): 1102.     CrossRef
  • Cellular interplay between cardiomyocytes and non-myocytes in diabetic cardiomyopathy
    Ren Jie Phang, Rebecca H Ritchie, Derek J Hausenloy, Jarmon G Lees, Shiang Y Lim
    Cardiovascular Research.2023; 119(3): 668.     CrossRef
  • Mitochondrial miRNA as epigenomic signatures: Visualizing aging-associated heart diseases through a new lens
    Jasvinder Singh Bhatti, Naina Khullar, Rajesh Vijayvergiya, Umashanker Navik, Gurjit Kaur Bhatti, P. Hemachandra Reddy
    Ageing Research Reviews.2023; 86: 101882.     CrossRef
  • Eucommiae Folium and Active Compounds Protect Against Mitochondrial Dysfunction-Calcium Overload in Epileptic Hippocampal Neurons Through the Hypertrophic Cardiomyopathy Pathway
    Shuai-nan Zhang, Hong-mei Li, Qi Liu, Xu-zhao Li, Wu-de Yang, Ying Zhou
    Neurochemical Research.2023; 48(9): 2674.     CrossRef
  • Speckle-tracking echocardiography provides sensitive measurements of subtle early alterations associated with cardiac dysfunction in T2DM rats
    Yanchao Qi, Zhiyan Chen, Bingyan Guo, Zhe Liu, Lijie Wang, Suyun Liu, Lixiang Xue, Meifang Ma, Yajuan Yin, Yongjun Li, Gang Liu
    BMC Cardiovascular Disorders.2023;[Epub]     CrossRef
  • Novel insights into the role of mitochondria in diabetic cardiomyopathy: molecular mechanisms and potential treatments
    Fumin Zhi, Qian Zhang, Li Liu, Xing Chang, Hongtao Xu
    Cell Stress and Chaperones.2023; 28(6): 641.     CrossRef
  • Transcription factor EB: A potential integrated network regulator in metabolic-associated cardiac injury
    Weixing Wen, Haoxiao Zheng, Weiwen Li, Guolin Huang, Peng Chen, Xiaolin Zhu, Yue Cao, Jiahuan Li, Xiaohui Huang, Yuli Huang
    Metabolism.2023; 147: 155662.     CrossRef
  • Role of STIM1 in the Regulation of Cardiac Energy Substrate Preference
    Panpan Liu, Zhuli Yang, Youjun Wang, Aomin Sun
    International Journal of Molecular Sciences.2023; 24(17): 13188.     CrossRef
  • Mitochondrial dysfunction at the crossroad of cardiovascular diseases and cancer
    Carmine Rocca, Teresa Soda, Ernestina Marianna De Francesco, Marco Fiorillo, Francesco Moccia, Giuseppe Viglietto, Tommaso Angelone, Nicola Amodio
    Journal of Translational Medicine.2023;[Epub]     CrossRef
  • Triarylphosphonium compounds as effective vectors for mitochondria-targeted delivery systems: decoration strategies and prospects for clinical application
    T. N. Pashirova, A. V. Nemtarev, E. B. Souto, V. F. Mironov
    Russian Chemical Reviews.2023; 92(10): RCR5095.     CrossRef
  • Moderate- and High-Intensity Endurance Training Alleviate Diabetes-Induced Cardiac Dysfunction in Rats
    Sarah D’Haese, Maxim Verboven, Lize Evens, Dorien Deluyker, Ivo Lambrichts, BO Eijnde, Dominique Hansen, Virginie Bito
    Nutrients.2023; 15(18): 3950.     CrossRef
  • Alpha-lipoic acid enhances ischemic postconditioning-mediated improvement of myocardial infarction and apoptosis in diabetic rats with ischemia/reperfusion injury
    Sanaz Gholami, Reza Badalzadeh, Alireza Alihemmati
    Canadian Journal of Physiology and Pharmacology.2023; 101(12): 682.     CrossRef
  • Concurrent diabetes and heart failure: interplay and novel therapeutic approaches
    Qutuba G Karwi, Kim L Ho, Simran Pherwani, Ezra B Ketema, Qiuyu Sun, Gary D Lopaschuk
    Cardiovascular Research.2022; 118(3): 686.     CrossRef
  • Ca2+ mishandling and mitochondrial dysfunction: a converging road to prediabetic and diabetic cardiomyopathy
    Carolina Jaquenod De Giusti, Julieta Palomeque, Alicia Mattiazzi
    Pflügers Archiv - European Journal of Physiology.2022; 474(1): 33.     CrossRef
  • Double-edge sword roles of iron in driving energy production versus instigating ferroptosis
    Shuping Zhang, Wei Xin, Gregory J. Anderson, Ruibin Li, Ling Gao, Shuguang Chen, Jiajun Zhao, Sijin Liu
    Cell Death & Disease.2022;[Epub]     CrossRef
  • Differential remodelling of mitochondrial subpopulations and mitochondrial dysfunction are a feature of early stage diabetes
    Bodour S. Rajab, Sarah Kassab, Connor D. Stonall, Hussam Daghistani, Stephen Gibbons, Mamas Mamas, David Smith, Aleksandr Mironov, Zainab AlBalawi, Yin Hua Zhang, Florence Baudoin, Min Zi, Sukhpal Prehar, Elizabeth J. Cartwright, Ashraf Kitmitto
    Scientific Reports.2022;[Epub]     CrossRef
  • GlyNAC (Glycine and N-Acetylcysteine) Supplementation Improves Impaired Mitochondrial Fuel Oxidation and Lowers Insulin Resistance in Patients with Type 2 Diabetes: Results of a Pilot Study
    Rajagopal V. Sekhar
    Antioxidants.2022; 11(1): 154.     CrossRef
  • Glucose-derived posttranslational modification in cardiovascular disease
    Michael Lehrke, Julia Moellmann, Florian Kahles, Nikolaus Marx
    Molecular Aspects of Medicine.2022; 86: 101084.     CrossRef
  • Mitochondrial Implications in Cardiovascular Aging and Diseases: The Specific Role of Mitochondrial Dynamics and Shifts
    Anastasia V. Poznyak, Tatiana V. Kirichenko, Evgeny E. Borisov, Nikolay K. Shakhpazyan, Andrey G. Kartuesov, Alexander N. Orekhov
    International Journal of Molecular Sciences.2022; 23(6): 2951.     CrossRef
  • Editorial: Management of Diabetes and its Complications: A Focus on Endothelial Dysfunction
    Shanhu Qiu, Jianhua Ma, Tongzhi Wu
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Alternative autophagy: mechanisms and roles in different diseases
    Hong Feng, Nian Wang, Nan Zhang, Hai-han Liao
    Cell Communication and Signaling.2022;[Epub]     CrossRef
  • Mitochondria-Mediated Cardiovascular Benefits of Sodium-Glucose Co-Transporter 2 Inhibitors
    Siarhei A. Dabravolski, Alexander D. Zhuravlev, Andrey G. Kartuesov, Evgeny E. Borisov, Vasily N. Sukhorukov, Alexander N. Orekhov
    International Journal of Molecular Sciences.2022; 23(10): 5371.     CrossRef
  • Animal Models of Dysregulated Cardiac Metabolism
    Heiko Bugger, Nikole J. Byrne, E. Dale Abel
    Circulation Research.2022; 130(12): 1965.     CrossRef
  • Mitochondrial Dynamics and Mitophagy in Cardiometabolic Disease
    Jianguo Lin, Jinlong Duan, Qingqing Wang, Siyu Xu, Simin Zhou, Kuiwu Yao
    Frontiers in Cardiovascular Medicine.2022;[Epub]     CrossRef
  • Perspectives for Forkhead box transcription factors in diabetic cardiomyopathy: Their therapeutic potential and possible effects of salvianolic acids
    Ronghui Han, Hemeng Huang, Weiyi Xia, Jingjin Liu, Hui Luo, Jing Tang, Zhengyuan Xia
    Frontiers in Cardiovascular Medicine.2022;[Epub]     CrossRef
  • Molecular and cellular mechanisms in diabetic heart failure: Potential therapeutic targets
    Misganaw Asmamaw Mengstie, Endeshaw Chekol Abebe, Awgichew Behaile Teklemariam, Anemut Tilahun Mulu, Assefa Agegnehu Teshome, Edgeit Abebe Zewde, Zelalem Tilahun Muche, Muluken Teshome Azezew
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Effect of Chronic Treatment with Uridine on Cardiac Mitochondrial Dysfunction in the C57BL/6 Mouse Model of High-Fat Diet–Streptozotocin-Induced Diabetes
    Natalia V. Belosludtseva, Vlada S. Starinets, Irina B. Mikheeva, Maxim N. Belosludtsev, Mikhail V. Dubinin, Galina D. Mironova, Konstantin N. Belosludtsev
    International Journal of Molecular Sciences.2022; 23(18): 10633.     CrossRef
  • FGF21–Sirtuin 3 Axis Confers the Protective Effects of Exercise Against Diabetic Cardiomyopathy by Governing Mitochondrial Integrity
    Leigang Jin, Leiluo Geng, Lei Ying, Lingling Shu, Kevin Ye, Ranyao Yang, Yan Liu, Yao Wang, Yin Cai, Xue Jiang, Qin Wang, Xingqun Yan, Boya Liao, Jie Liu, Fuyu Duan, Gary Sweeney, Connie Wai Hong Woo, Yu Wang, Zhengyuan Xia, Qizhou Lian, Aimin Xu
    Circulation.2022; 146(20): 1537.     CrossRef
  • Novel Insights Into Molecular Mechanism of Mitochondria in Diabetic Cardiomyopathy
    Jing Bai, Chuanbin Liu, Pingjun Zhu, Yang Li
    Frontiers in Physiology.2021;[Epub]     CrossRef
  • Mitochondrial Dysfunction Increases Arrhythmic Triggers and Substrates; Potential Anti-arrhythmic Pharmacological Targets
    Khalil Saadeh, Ibrahim Talal Fazmin
    Frontiers in Cardiovascular Medicine.2021;[Epub]     CrossRef
  • Prostaglandin E receptor subtype 4 protects against diabetic cardiomyopathy by modulating cardiac fatty acid metabolism via FOXO1/CD36 signalling
    Fan Ying, Hao Liu, Eva Hoi Ching Tang, Ishan Lakhani, Ningning Liu, Zhengyuan Xia, Shiming Liu
    Biochemical and Biophysical Research Communications.2021; 548: 196.     CrossRef
  • Study of long non-coding RNA and mitochondrial dysfunction in diabetic rats
    Haytham K. Sultan, Wael M. El-Ayat, Azza H. AbouGhalia, Noha N. Lasheen, Amr S. Moustafa
    Tissue and Cell.2021; 71: 101516.     CrossRef
  • A Role of Glucose Overload in Diabetic Cardiomyopathy in Nonhuman Primates
    Xiu Wang, Shi Jin, Weina Hu, Gaetano Santulli
    Journal of Diabetes Research.2021; 2021: 1.     CrossRef
  • Dysregulation of circulating miRNAs promotes the pathogenesis of diabetes-induced cardiomyopathy
    Uzair Ahmed, Usman Ali Ashfaq, Muhammad Qasim, Imtiaz Ahmad, Hafiz Usman Ahmad, Muhammad Tariq, Muhammad Shareef Masoud, Saba Khaliq, Muhammad Younas Khan Barozai
    PLOS ONE.2021; 16(4): e0250773.     CrossRef
  • MicroRNAs Regulating Mitochondrial Function in Cardiac Diseases
    Guang-Qiong Zhang, Sheng-Quan Wang, Yan Chen, Ling-Yun Fu, Yi-Ni Xu, Ling Li, Ling Tao, Xiang-Chun Shen
    Frontiers in Pharmacology.2021;[Epub]     CrossRef
  • Effects of omega-3 fatty acids and metformin combination on diabetic cardiomyopathy in rats through autophagic pathway
    Salma M. Eraky, Nehal M. Ramadan
    The Journal of Nutritional Biochemistry.2021; 97: 108798.     CrossRef
  • Adropin Alleviates Myocardial Fibrosis in Diabetic Cardiomyopathy Rats: A Preliminary Study
    Mao Liu, Jiao Ai, Zhuang Shuai, Kai Tang, Zongyu Li, Yin Huang
    Frontiers in Cardiovascular Medicine.2021;[Epub]     CrossRef
  • Fibrosis of the diabetic heart: Clinical significance, molecular mechanisms, and therapeutic opportunities
    Izabela Tuleta, Nikolaos G. Frangogiannis
    Advanced Drug Delivery Reviews.2021; 176: 113904.     CrossRef
  • Effect of the MPT Pore Inhibitor Alisporivir on the Development of Mitochondrial Dysfunction in the Heart Tissue of Diabetic Mice
    Natalia V. Belosludtseva, Vlada S. Starinets, Irina B. Mikheeva, Dmitriy A. Serov, Maxim E. Astashev, Maxim N. Belosludtsev, Mikhail V. Dubinin, Konstantin N. Belosludtsev
    Biology.2021; 10(9): 839.     CrossRef
  • Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy
    Alex M. Parker, Mitchel Tate, Darnel Prakoso, Minh Deo, Andrew M. Willis, David M. Nash, Daniel G. Donner, Simon Crawford, Helen Kiriazis, Cesare Granata, Melinda T. Coughlan, Miles J. De Blasio, Rebecca H. Ritchie
    Frontiers in Physiology.2021;[Epub]     CrossRef
  • Radiation‑induced dysfunction of energy metabolism in the heart results in the fibrosis of cardiac tissues
    Peng Xu, Yali Yi, Yijing Luo, Zhicheng Liu, Yilin Xu, Jing Cai, Zhimin Zeng, Anwen Liu
    Molecular Medicine Reports.2021;[Epub]     CrossRef
  • Heart Failure and Diabetes: Perspective of a Dangerous Association
    Liliana E. Favaloro, Roxana D. Ratto, Carla Musso
    Current Hypertension Reviews.2021; 17(2): 85.     CrossRef
  • CTRP9 Mediates Protective Effects in Cardiomyocytes via AMPK- and Adiponectin Receptor-Mediated Induction of Anti-Oxidant Response
    Bernd Niemann, Ling Li, Dorothee Siegler, Benedikt H. Siegler, Fabienne Knapp, Jakob Hanna, Muhammad Aslam, Michael Kracht, Rainer Schulz, Susanne Rohrbach
    Cells.2020; 9(5): 1229.     CrossRef
  • The Hippo Pathway Orchestrates Mitochondrial Quality Control: A Novel Focus on Cardiovascular Diseases
    Ying Tan, Cai Lei, Huifang Tang, Xiao Zhu, Guanghui Yi
    DNA and Cell Biology.2020; 39(9): 1494.     CrossRef
  • Adeno-Associated Viral Transfer of Glyoxalase-1 Blunts Carbonyl and Oxidative Stresses in Hearts of Type 1 Diabetic Rats
    Fadhel A. Alomar, Abdullah Al-Rubaish, Fahad Al-Muhanna, Amein K. Al-Ali, JoEllyn McMillan, Jaipaul Singh, Keshore R. Bidasee
    Antioxidants.2020; 9(7): 592.     CrossRef
  • Loss of function of transcription factor EB remodels lipid metabolism and cell death pathways in the cardiomyocyte
    Purvi C. Trivedi, Jordan J. Bartlett, Angella Mercer, Logan Slade, Marc Surette, Andrea Ballabio, Stephane Flibotte, Bahira Hussein, Brian Rodrigues, Petra C. Kienesberger, Thomas Pulinilkunnil
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2020; 1866(10): 165832.     CrossRef
  • Rescue of myocardial energetic dysfunction in diabetes through the correction of mitochondrial hyperacetylation by honokiol
    Matthew Kerr, Jack J. Miller, Dharendra Thapa, Sophie Stiewe, Kerstin N. Timm, Claudia N. Montes Aparicio, Iain Scott, Damian J. Tyler, Lisa C. Heather
    JCI Insight.2020;[Epub]     CrossRef
  • Diabetes Mellitus, Mitochondrial Dysfunction and Ca2+-Dependent Permeability Transition Pore
    Konstantin N. Belosludtsev, Natalia V. Belosludtseva, Mikhail V. Dubinin
    International Journal of Molecular Sciences.2020; 21(18): 6559.     CrossRef
  • Effects of Standardized Green Tea Extract and Its Main Component, EGCG, on Mitochondrial Function and Contractile Performance of Healthy Rat Cardiomyocytes
    Rocchina Vilella, Gianluca Sgarbi, Valeria Naponelli, Monia Savi, Leonardo Bocchi, Francesca Liuzzi, Riccardo Righetti, Federico Quaini, Caterina Frati, Saverio Bettuzzi, Giancarlo Solaini, Donatella Stilli, Federica Rizzi, Alessandra Baracca
    Nutrients.2020; 12(10): 2949.     CrossRef
  • Diabetic cardiomyopathy: definition, diagnosis criteria, treatment directions and prevention of heart failure
    N. A. Koziolova, P. G. Karavaev, A. S. Veklich
    South Russian Journal of Therapeutic Practice.2020; 1(2): 93.     CrossRef
  • Adiponectin protects HL-1 cardiomyocytes against rotenone-induced cytotoxicity through AMPK activation
    Biao Li, Baojian Zhang, Na Liu, Keke Wu, Yingxu Ma, Wanyun Zuo, Zuodong Ning, Yaozhong Liu, Chao Sun, Yichao Xiao, Tao Tu, Qiming Liu
    Toxicology Letters.2020; 335: 82.     CrossRef
  • Nutrient Sensor mTOR and OGT: Orchestrators of Organelle Homeostasis in Pancreatic β-Cells
    Nicholas Esch, Seokwon Jo, Mackenzie Moore, Emilyn U. Alejandro, Yingke Xu
    Journal of Diabetes Research.2020; 2020: 1.     CrossRef
  • Where Does Metformin Stand in Modern Day Management of Type 2 Diabetes?
    Ehtasham Ahmad, Jack Sargeant, Francesco Zaccardi, Kamlesh Khunti, David Webb, Melanie Davies
    Pharmaceuticals.2020; 13(12): 427.     CrossRef
Original Article
Basic Research
Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy
Chang-Yun Woo, Ji Yeon Baek, Ah-Ram Kim, Chung Hwan Hong, Ji Eun Yoon, Hyoun Sik Kim, Hyun Ju Yoo, Tae-Sik Park, Ranjan Kc, Ki-Up Lee, Eun Hee Koh
Diabetes Metab J. 2020;44(4):581-591.   Published online November 4, 2019
DOI: https://doi.org/10.4093/dmj.2019.0063
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AbstractAbstract PDFPubReader   ePub   
Background

Ceramides are associated with metabolic complications including diabetic nephropathy in patients with diabetes. Recent studies have reported that podocytes play a pivotal role in the progression of diabetic nephropathy. Also, mitochondrial dysfunction is known to be an early event in podocyte injury. Thus, we tested the hypothesis that ceramide accumulation in podocytes induces mitochondrial damage through reactive oxygen species (ROS) production in patients with diabetic nephropathy.

Methods

We used Otsuka Long Evans Tokushima Fatty (OLETF) rats and high-fat diet (HFD)-fed mice. We fed the animals either a control- or a myriocin-containing diet to evaluate the effects of the ceramide. Also, we assessed the effects of ceramide on intracellular ROS generation and on podocyte autophagy in cultured podocytes.

Results

OLETF rats and HFD-fed mice showed albuminuria, histologic features of diabetic nephropathy, and podocyte injury, whereas myriocin treatment effectively treated these abnormalities. Cultured podocytes exposed to agents predicted to be risk factors (high glucose, high free fatty acid, and angiotensin II in combination [GFA]) showed an increase in ceramide accumulation and ROS generation in podocyte mitochondria. Pretreatment with myriocin reversed GFA-induced mitochondrial ROS generation and prevented cell death. Myriocin-pretreated cells were protected from GFA-induced disruption of mitochondrial integrity.

Conclusion

We showed that mitochondrial ceramide accumulation may result in podocyte damage through ROS production. Therefore, this signaling pathway could become a pharmacological target to abate the development of diabetic kidney disease.

Citations

Citations to this article as recorded by  
  • Interplay of lipid metabolism and inflammation in podocyte injury
    Zilv Luo, Zhaowei Chen, Jijia Hu, Guohua Ding
    Metabolism.2024; 150: 155718.     CrossRef
  • Associations of plasma sphingolipids with measures of insulin sensitivity, β-cell function, and incident diabetes in Japanese Americans
    Ji Cheol Bae, Pandora L. Wander, Rozenn N. Lemaitre, Amanda M. Fretts, Colleen M. Sitlani, Hai H. Bui, Melissa K. Thomas, Donna Leonetti, Wilfred Y. Fujimoto, Edward J. Boyko, Kristina M. Utzschneider
    Nutrition, Metabolism and Cardiovascular Diseases.2024; 34(3): 633.     CrossRef
  • A review of the mechanisms of abnormal ceramide metabolism in type 2 diabetes mellitus, Alzheimer’s disease, and their co-morbidities
    Yun Pan, Jieying Li, Panjie Lin, Lihua Wan, Yiqian Qu, Lingyong Cao, Lei Wang
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • Ceramides and mitochondrial homeostasis
    Song Ding, Guorui Li, Tinglv Fu, Tianyu Zhang, Xiao Lu, Ning Li, Qing Geng
    Cellular Signalling.2024; 117: 111099.     CrossRef
  • Reduced sphingolipid biosynthesis modulates proteostasis networks to enhance longevity
    Nathaniel L. Hepowit, Eric Blalock, Sangderk Lee, Kimberly M. Bretland, Jason A. MacGurn, Robert C. Dickson
    Aging.2023; 15(2): 472.     CrossRef
  • Protective effect of natural products in the metabolic-associated kidney diseases via regulating mitochondrial dysfunction
    Peng Liu, Yao Chen, Jing Xiao, Wenhui Zhu, Xiaoming Yan, Ming Chen
    Frontiers in Pharmacology.2023;[Epub]     CrossRef
  • BCAA insufficiency leads to premature ovarian insufficiency via ceramide‐induced elevation of ROS
    Xiao Guo, Yuemeng Zhu, Lu Guo, Yiwen Qi, Xiaocheng Liu, Jinhui Wang, Jiangtao Zhang, Linlin Cui, Yueyang Shi, Qichu Wang, Cenxi Liu, Guangxing Lu, Yilian Liu, Tao Li, Shangyu Hong, Yingying Qin, Xuelian Xiong, Hao Wu, Lin Huang, He Huang, Chao Gu, Bin Li,
    EMBO Molecular Medicine.2023;[Epub]     CrossRef
  • Chinese herbal medicine and its active compounds in attenuating renal injury via regulating autophagy in diabetic kidney disease
    Peng Liu, Wenhui Zhu, Yang Wang, Guijie Ma, Hailing Zhao, Ping Li
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Integrated gas chromatography‐mass spectrometry and ultra‐high‐performance liquid chromatography‐mass spectrometry renal metabolomics and lipidomics deciphered the metabolic regulation mechanism of Gushudan on kidney‐yang‐deficiency‐syndrome rats
    Qing Lu, Jing Zhang, Ling Xin, Yanwei Lou, Feng Qin, Longshan Zhao, Zhili Xiong
    Journal of Separation Science.2023;[Epub]     CrossRef
  • Advances in the pharmacological study of Chinese herbal medicine to alleviate diabetic nephropathy by improving mitochondrial oxidative stress
    Ming Chen, Yao Chen, Wenhui Zhu, Xiaoming Yan, Jing Xiao, Peiqing Zhang, Peng Liu, Ping Li
    Biomedicine & Pharmacotherapy.2023; 165: 115088.     CrossRef
  • Rodent models to study type 1 and type 2 diabetes induced human diabetic nephropathy
    Amit Talukdar, Mandira Basumatary
    Molecular Biology Reports.2023; 50(9): 7759.     CrossRef
  • Art2 mediates selective endocytosis of methionine transporters during adaptation to sphingolipid depletion
    Nathaniel L. Hepowit, Bradley Moon, Adam C. Ebert, Robert C. Dickson, Jason A. MacGurn
    Journal of Cell Science.2023;[Epub]     CrossRef
  • Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease
    Alla Mitrofanova, Sandra Merscher, Alessia Fornoni
    Nature Reviews Nephrology.2023; 19(10): 629.     CrossRef
  • Research progress of autophagy in pathogenesis of diabetes nephropathy
    Shengnan Zeng, Ying Li
    Diabetic Nephropathy.2023; 3(3): 51.     CrossRef
  • Lipidomic approaches to dissect dysregulated lipid metabolism in kidney disease
    Judy Baek, Chenchen He, Farsad Afshinnia, George Michailidis, Subramaniam Pennathur
    Nature Reviews Nephrology.2022; 18(1): 38.     CrossRef
  • Podocyte Bioenergetics in the Development of Diabetic Nephropathy: The Role of Mitochondria
    Irena Audzeyenka, Agnieszka Bierżyńska, Abigail C Lay
    Endocrinology.2022;[Epub]     CrossRef
  • Acylcarnitines: Can They Be Biomarkers of Diabetic Nephropathy?
    Xiaodie Mu, Min Yang, Peiyao Ling, Aihua Wu, Hua Zhou, Jingting Jiang
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 247.     CrossRef
  • Research Progress on Natural Products’ Therapeutic Effects on Atrial Fibrillation by Regulating Ion Channels
    Jinshan He, Sicong Li, Yumeng Ding, Yujia Tong, Xuebin Li, Simona Saponara
    Cardiovascular Therapeutics.2022; 2022: 1.     CrossRef
  • Mechanisms of podocyte injury and implications for diabetic nephropathy
    Federica Barutta, Stefania Bellini, Gabriella Gruden
    Clinical Science.2022; 136(7): 493.     CrossRef
  • A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury
    Norishi Ueda
    International Journal of Molecular Sciences.2022; 23(7): 4010.     CrossRef
  • Implications of Sphingolipid Metabolites in Kidney Diseases
    Shamroop kumar Mallela, Sandra Merscher, Alessia Fornoni
    International Journal of Molecular Sciences.2022; 23(8): 4244.     CrossRef
  • Role of ceramides in the pathogenesis of diabetes mellitus and its complications
    Nawajes Mandal, Richard Grambergs, Koushik Mondal, Sandip K. Basu, Faiza Tahia, Sam Dagogo-Jack
    Journal of Diabetes and its Complications.2021; 35(2): 107734.     CrossRef
  • Rotten to the Cortex: Ceramide-Mediated Lipotoxicity in Diabetic Kidney Disease
    Rebekah J. Nicholson, Marcus G. Pezzolesi, Scott A. Summers
    Frontiers in Endocrinology.2021;[Epub]     CrossRef
  • Enhancing lifespan of budding yeast by pharmacological lowering of amino acid pools
    Nathaniel L. Hepowit, Jessica K. A. Macedo, Lyndsay E. A. Young, Ke Liu, Ramon C. Sun, Jason A. MacGurn, Robert C. Dickson
    Aging.2021; 13(6): 7846.     CrossRef
  • New insights into renal lipid dysmetabolism in diabetic kidney disease
    Alla Mitrofanova, George Burke, Sandra Merscher, Alessia Fornoni
    World Journal of Diabetes.2021; 12(5): 524.     CrossRef
  • Excessively Enlarged Mitochondria in the Kidneys of Diabetic Nephropathy
    Kiyoung Kim, Eun-Young Lee
    Antioxidants.2021; 10(5): 741.     CrossRef
  • Mechanistic insights into the role of serum-glucocorticoid kinase 1 in diabetic nephropathy: A systematic review
    Saba Noor, Taj Mohammad, Gulam M. Ashraf, Joviana Farhat, Anwar L. Bilgrami, Mathew Suji Eapen, Sukhwinder Singh Sohal, Dharmendra Kumar Yadav, Md Imtaiyaz Hassan
    International Journal of Biological Macromolecules.2021; 193: 562.     CrossRef
  • The Updates of Podocyte Lipid Metabolism in Proteinuric Kidney Disease
    Yu Sun, Sijia Cui, Yunfeng Hou, Fan Yi
    Kidney Diseases.2021; 7(6): 438.     CrossRef
  • Saturated fatty acids induce insulin resistance in podocytes through inhibition of IRS1 via activation of both IKKβ and mTORC1
    Benoit Denhez, Marina Rousseau, Crysta Spino, David-Alexandre Dancosst, Marie-Ève Dumas, Andréanne Guay, Farah Lizotte, Pedro Geraldes
    Scientific Reports.2020;[Epub]     CrossRef
Review
Others
Mitochondrial Toxins and Healthy Lifestyle Meet at the Crossroad of Hormesis
Yu-Mi Lee, Duk-Hee Lee
Diabetes Metab J. 2019;43(5):568-577.   Published online October 24, 2019
DOI: https://doi.org/10.4093/dmj.2019.0143
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AbstractAbstract PDFPubReader   

Mitochondrial function is crucial for the maintenance of cellular homeostasis under physiological and stress conditions. Thus, chronic exposure to environmental chemicals that affect mitochondrial function can have harmful effects on humans. We argue that the concept of hormesis should be revisited to explain the non-linear responses to mitochondrial toxins at a low-dose range and develop practical methods to protect humans from the negative effects of mitochondrial toxins. Of the most concern to humans are lipophilic chemical mixtures and heavy metals, owing to their physical properties. Even though these chemicals tend to demonstrate no safe level in humans, a non-linear dose-response has been also observed. Stress response activation, i.e., hormesis, can explain this non-linearity. Recently, hormesis has reemerged as a unifying concept because diverse stressors can induce similar stress responses. Besides potentially harmful environmental chemicals, healthy lifestyle interventions such as exercise, calorie restriction (especially glucose), cognitive stimulation, and phytochemical intake also activate stress responses. This conceptual link can lead to the development of practical methods that counterbalance the harm of mitochondrial toxins. Unlike chemical hormesis with its safety issues, the activation of stress responses via lifestyle modification can be safely used to combat the negative effects of mitochondrial toxins.

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  • Rules of Heliogeomagnetics Diversely Coordinating Biological Rhythms and Promoting Human Health
    Kuniaki Otsuka, Germaine Cornelissen, Andi Weydahl, Denis Gubin, Larry A. Beaty, Masatoshi Murase
    Applied Sciences.2023; 13(2): 951.     CrossRef
  • Can lipophilic pollutants in adipose tissue explain weight change‐related risk in type 2 diabetes mellitus?
    Duk‐Hee Lee, In‐Kyu Lee
    Journal of Diabetes Investigation.2023; 14(4): 528.     CrossRef
  • Hormetic Effects of Cerium, Lanthanum and Their Combination at Sub-micromolar Concentrations in Sea Urchin Sperm
    Giovanni Pagano, Antonios Apostolos Brouziotis, Daniel Lyons, Ivana Čarapar, Rahime Oral, Serkan Tez, Philippe J. Thomas, Franca Tommasi, Giovanni Libralato, Marco Guida, Marco Trifuoggi
    Bulletin of Environmental Contamination and Toxicology.2023;[Epub]     CrossRef
  • Mitochondria: It is all about energy
    Amaloha Casanova, Anne Wevers, Santiago Navarro-Ledesma, Leo Pruimboom
    Frontiers in Physiology.2023;[Epub]     CrossRef
  • Type 2 Diabetes Induced by Changes in Proteomic Profiling of Zebrafish Chronically Exposed to a Mixture of Organochlorine Pesticides at Low Concentrations
    Yan Gao, Hyojin Lee, Sangkyu Lee, Ki-Tae Kim
    International Journal of Environmental Research and Public Health.2022; 19(9): 4991.     CrossRef
  • Effect of Low-Dose Persistent Organic Pollutants on Mitochondrial Function: Human and in Vitro Evidence
    Se-A Kim, Hoyul Lee, Sung-Mi Park, Mi-Jin Kim, Yu-Mi Lee, Young-Ran Yoon, Hyun-Kyung Lee, Hyo-Bang Moon, In-Kyu Lee, Duk-Hee Lee
    Diabetes & Metabolism Journal.2022; 46(4): 592.     CrossRef
  • Can Environmental Pollutants Be a Factor Linking Obesity and COVID-19?
    Duk-Hee Lee
    Journal of Korean Medical Science.2021;[Epub]     CrossRef
  • Intensive weight loss and cognition: The dynamics of persistent organic pollutants in adipose tissue can explain the unexpected results from the Action for Health in Diabetes (Look AHEAD) study
    Yu‐Mi Lee, Sun‐Hee Park, Duk‐Hee Lee
    Alzheimer's & Dementia.2020; 16(4): 696.     CrossRef
  • Lipophilic Environmental Chemical Mixtures Released During Weight‐Loss: The Need to Consider Dynamics
    Duk‐Hee Lee, David R Jacobs, Lars Lind, P. Monica Lind
    BioEssays.2020;[Epub]     CrossRef
  • Environmental toxicology and ecotoxicology: How clean is clean? Rethinking dose-response analysis
    Evgenios Agathokleous, Edward J. Calabrese
    Science of The Total Environment.2020; 746: 138769.     CrossRef
Sulwon Lecture 2018
Pathophysiology
Mitochondrial Dysfunction in Adipocytes as a Primary Cause of Adipose Tissue Inflammation
Chang-Yun Woo, Jung Eun Jang, Seung Eun Lee, Eun Hee Koh, Ki-Up Lee
Diabetes Metab J. 2019;43(3):247-256.   Published online March 27, 2019
DOI: https://doi.org/10.4093/dmj.2018.0221
  • 8,472 View
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  • 69 Web of Science
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AbstractAbstract PDFPubReader   

Adipose tissue inflammation is considered a major contributing factor in the development of obesity-associated insulin resistance and cardiovascular diseases. However, the cause of adipose tissue inflammation is presently unclear. The role of mitochondria in white adipocytes has long been neglected because of their low abundance. However, recent evidence suggests that mitochondria are essential for maintaining metabolic homeostasis in white adipocytes. In a series of recent studies, we found that mitochondrial function in white adipocytes is essential to the synthesis of adiponectin, which is the most abundant adipokine synthesized from adipocytes, with many favorable effects on metabolism, including improvement of insulin sensitivity and reduction of atherosclerotic processes and systemic inflammation. From these results, we propose a new hypothesis that mitochondrial dysfunction in adipocytes is a primary cause of adipose tissue inflammation and compared this hypothesis with a prevailing concept that “adipose tissue hypoxia” may underlie adipose tissue dysfunction in obesity. Recent studies have emphasized the role of the mitochondrial quality control mechanism in maintaining mitochondrial function. Future studies are warranted to test whether an inadequate mitochondrial quality control mechanism is responsible for mitochondrial dysfunction in adipocytes and adipose tissue inflammation.

Citations

Citations to this article as recorded by  
  • Prolonged Endurance Exercise Increases Macrophage Content and Mitochondrial Respiration in Adipose Tissue in Trained Men
    Ronni Eg Sahl, Ioanna Patsi, Mikkel Thunestvedt Hansen, Tue Rømer, Jacob Frandsen, Hanne Kruuse Rasmusen, Arthur Ingersen, Steen Seier Poulsen, Flemming Dela, Steen Larsen, Jørn Wulff Helge
    The Journal of Clinical Endocrinology & Metabolism.2024; 109(2): e799.     CrossRef
  • Diabetes Mellitus, Energy Metabolism, and COVID-19
    Caterina Conte, Elisa Cipponeri, Michael Roden
    Endocrine Reviews.2024; 45(2): 281.     CrossRef
  • The Role of Ion-Transporting Proteins in Human Disease
    Yoshinori Marunaka
    International Journal of Molecular Sciences.2024; 25(3): 1726.     CrossRef
  • The Role of Obesity in Type 2 Diabetes Mellitus—An Overview
    Preethi Chandrasekaran, Ralf Weiskirchen
    International Journal of Molecular Sciences.2024; 25(3): 1882.     CrossRef
  • The Metabolic Syndrome, a Human Disease
    Marià Alemany
    International Journal of Molecular Sciences.2024; 25(4): 2251.     CrossRef
  • Inflammation‐mediated metabolic regulation in adipose tissue
    Shujie Xu, Feng Lu, Jianhua Gao, Yi Yuan
    Obesity Reviews.2024;[Epub]     CrossRef
  • Could very low-calorie ketogenic diets turn off low grade inflammation in obesity? Emerging evidence
    Luigi Barrea, Massimiliano Caprio, Mikiko Watanabe, Giuseppe Cammarata, Alessandra Feraco, Giovanna Muscogiuri, Ludovica Verde, Annamaria Colao, Silvia Savastano
    Critical Reviews in Food Science and Nutrition.2023; 63(26): 8320.     CrossRef
  • The emergent role of mitochondrial RNA modifications in metabolic alterations
    Hatim Boughanem, Yvonne Böttcher, João Tomé‐Carneiro, María‐Carmen López de las Hazas, Alberto Dávalos, Akin Cayir, Manuel Macias‐González
    WIREs RNA.2023;[Epub]     CrossRef
  • Age‐associated adipose tissue inflammation promotes monocyte chemotaxis and enhances atherosclerosis
    Jianrui Song, Diana Farris, Paola Ariza, Smriti Moorjani, Mita Varghese, Muriel Blin, Judy Chen, Daniel Tyrrell, Min Zhang, Kanakadurga Singer, Morgan Salmon, Daniel R. Goldstein
    Aging Cell.2023;[Epub]     CrossRef
  • Obesity, diabetes mellitus, and cardiometabolic risk: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2023
    Harold Edward Bays, Shagun Bindlish, Tiffany Lowe Clayton
    Obesity Pillars.2023; 5: 100056.     CrossRef
  • A role of STING signaling in obesity-induced lung inflammation
    Yong Qi, Zhuhua Wu, Dan Chen, Li Zhu, Yunlei Yang
    International Journal of Obesity.2023; 47(4): 325.     CrossRef
  • Estrogens in Adipose Tissue Physiology and Obesity-Related Dysfunction
    Alina Kuryłowicz
    Biomedicines.2023; 11(3): 690.     CrossRef
  • White Adipose Tissue Dysfunction: Pathophysiology and Emergent Measurements
    Natalia Santillana, Camila Astudillo-Guerrero, Amanda D’Espessailles, Gonzalo Cruz
    Nutrients.2023; 15(7): 1722.     CrossRef
  • Pleiotropic and multi-systemic actions of physical exercise on PGC-1α signaling during the aging process
    Ivo Vieira de Sousa Neto, Ana Paula Pinto, Vitor Rosetto Muñoz, Rita de Cássia Marqueti, José Rodrigo Pauli, Eduardo Rochete Ropelle, Adelino Sanchez Ramos da Silva
    Ageing Research Reviews.2023; 87: 101935.     CrossRef
  • The impact of metabolic endotoxaemia on the browning process in human adipocytes
    Farah Omran, Alice M. Murphy, Awais Z. Younis, Ioannis Kyrou, Jana Vrbikova, Vojtech Hainer, Petra Sramkova, Martin Fried, Graham Ball, Gyanendra Tripathi, Sudhesh Kumar, Philip G. McTernan, Mark Christian
    BMC Medicine.2023;[Epub]     CrossRef
  • Molecular Mechanisms of Obesity-Induced Development of Insulin Resistance and Promotion of Amyloid-β Accumulation: Dietary Therapy Using Weak Organic Acids via Improvement of Lowered Interstitial Fluid pH
    Yoshinori Marunaka
    Biomolecules.2023; 13(5): 779.     CrossRef
  • From Obesity-Induced Low-Grade Inflammation to Lipotoxicity and Mitochondrial Dysfunction: Altered Multi-Crosstalk between Adipose Tissue and Metabolically Active Organs
    Gina Cavaliere, Fabiano Cimmino, Giovanna Trinchese, Angela Catapano, Lidia Petrella, Margherita D’Angelo, Lucio Lucchin, Maria Pina Mollica
    Antioxidants.2023; 12(6): 1172.     CrossRef
  • Receptor for the Advanced Glycation End Products (RAGE) Pathway in Adipose Tissue Metabolism
    Klaudia Gutowska, Krzysztof Czajkowski, Alina Kuryłowicz
    International Journal of Molecular Sciences.2023; 24(13): 10982.     CrossRef
  • Aerobic and Resistance Training Attenuate Differently Knee Joint Damage Caused by a High-Fat–High-Sucrose Diet in a Rat Model
    Nada Abughazaleh, Kevin Boldt, Jaqueline Lourdes Rios, Stela Marcia Mattiello, Kelsey H. Collins, Ruth-Anne Seerattan, Walter Herzog
    CARTILAGE.2023;[Epub]     CrossRef
  • Exercise mitigates age-related metabolic diseases by improving mitochondrial dysfunction
    Dandan Jia, Zhenjun Tian, Ru Wang
    Ageing Research Reviews.2023; 91: 102087.     CrossRef
  • Mitochondrial dynamics and metabolism across skin cells: implications for skin homeostasis and aging
    Ines Martic, Federica Papaccio, Barbara Bellei, Maria Cavinato
    Frontiers in Physiology.2023;[Epub]     CrossRef
  • Influence of Breastfeeding on the State of Meta-Inflammation in Obesity—A Narrative Review
    Dominika Mazur, Małgorzata Satora, Anna K. Rekowska, Zuzanna Kabała, Aleksandra Łomża, Żaneta Kimber-Trojnar, Bożena Leszczyńska-Gorzelak
    Current Issues in Molecular Biology.2023; 45(11): 9003.     CrossRef
  • AGER-1 Long Non-Coding RNA Levels Correlate with the Expression of the Advanced Glycosylation End-Product Receptor, a Regulator of the Inflammatory Response in Visceral Adipose Tissue of Women with Obesity and Type 2 Diabetes Mellitus
    Klaudia Gutowska, Krzysztof Koźniewski, Michał Wąsowski, Marta Izabela Jonas, Zbigniew Bartoszewicz, Wojciech Lisik, Maurycy Jonas, Artur Binda, Paweł Jaworski, Wiesław Tarnowski, Bartłomiej Noszczyk, Monika Puzianowska-Kuźnicka, Krzysztof Czajkowski, Ali
    International Journal of Molecular Sciences.2023; 24(24): 17447.     CrossRef
  • Pharmacological treatment with FGF21 strongly improves plasma cholesterol metabolism to reduce atherosclerosis
    Cong Liu, Milena Schönke, Enchen Zhou, Zhuang Li, Sander Kooijman, Mariëtte R Boon, Mikael Larsson, Kristina Wallenius, Niek Dekker, Louise Barlind, Xiao-Rong Peng, Yanan Wang, Patrick C N Rensen
    Cardiovascular Research.2022; 118(2): 489.     CrossRef
  • Obesity-Related Adipose Tissue Remodeling in the Light of Extracellular Mitochondria Transfer
    Simon Lecoutre, Karine Clément, Isabelle Dugail
    International Journal of Molecular Sciences.2022; 23(2): 632.     CrossRef
  • IL-4 polarized human macrophage exosomes control cardiometabolic inflammation and diabetes in obesity
    Tuan Anh Phu, Martin Ng, Ngan K. Vu, Laura Bouchareychas, Robert L. Raffai
    Molecular Therapy.2022; 30(6): 2274.     CrossRef
  • Insulin-inducible THRSP maintains mitochondrial function and regulates sphingolipid metabolism in human adipocytes
    Maria A. Ahonen, Marcus Höring, Van Dien Nguyen, Sami Qadri, Juuso H. Taskinen, Meghana Nagaraj, Martin Wabitsch, Pamela Fischer-Posovszky, You Zhou, Gerhard Liebisch, P. A. Nidhina Haridas, Hannele Yki-Järvinen, Vesa M. Olkkonen
    Molecular Medicine.2022;[Epub]     CrossRef
  • Modulation of adipose inflammation by cellular retinoic acid-binding protein 1
    Chin-Wen Wei, Jennifer Nhieu, Yu-Lung Lin, Li-Na Wei
    International Journal of Obesity.2022; 46(10): 1759.     CrossRef
  • The Role of Adipokines in Pancreatic Cancer
    Qi Wang, Huizhi Wang, Yuntao Ding, Mengtian Wan, Min Xu
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Epigenetic Reprogramming of the Inflammatory Response in Obesity and Type 2 Diabetes
    Federica Zatterale, Gregory Alexander Raciti, Immacolata Prevenzano, Alessia Leone, Michele Campitelli, Veronica De Rosa, Francesco Beguinot, Luca Parrillo
    Biomolecules.2022; 12(7): 982.     CrossRef
  • Cellular Metabolism and Bioenergetic Function in Human Fibroblasts and Preadipocytes of Type 2 Familial Partial Lipodystrophy
    Cristina Algieri, Chiara Bernardini, Fabiana Trombetti, Elisa Schena, Augusta Zannoni, Monica Forni, Salvatore Nesci
    International Journal of Molecular Sciences.2022; 23(15): 8659.     CrossRef
  • Shared pathobiology identifies AMPK as a therapeutic target for obesity and autosomal dominant polycystic kidney disease
    Ioan-Andrei Iliuta, Xuewen Song, Lauren Pickel, Amirreza Haghighi, Ravi Retnakaran, James Scholey, Hoon-Ki Sung, Gregory R. Steinberg, York Pei
    Frontiers in Molecular Biosciences.2022;[Epub]     CrossRef
  • Hypoxia as a Double-Edged Sword to Combat Obesity and Comorbidities
    Ruwen Wang, Qin Sun, Xianmin Wu, Yiyin Zhang, Xiaorui Xing, Kaiqing Lin, Yue Feng, Mingqi Wang, Yibing Wang, Ru Wang
    Cells.2022; 11(23): 3735.     CrossRef
  • Macrophage and Adipocyte Mitochondrial Dysfunction in Obesity-Induced Metabolic Diseases
    Liwen Wang, Jie Hu, Haiyan Zhou
    The World Journal of Men's Health.2021; 39(4): 606.     CrossRef
  • ESRRA (estrogen related receptor alpha) is a critical regulator of intestinal homeostasis through activation of autophagic flux via gut microbiota
    Sup Kim, June-Young Lee, Seul Gi Shin, Jin Kyung Kim, Prashanta Silwal, Young Jae Kim, Na-Ri Shin, Pil Soo Kim, Minho Won, Sang-Hee Lee, Soo Yeon Kim, Miwa Sasai, Masahiro Yamamoto, Jin-Man Kim, Jin-Woo Bae, Eun-Kyeong Jo
    Autophagy.2021; 17(10): 2856.     CrossRef
  • GDF15 as a central mediator for integrated stress response and a promising therapeutic molecule for metabolic disorders and NASH
    Kook Hwan Kim, Myung-Shik Lee
    Biochimica et Biophysica Acta (BBA) - General Subjects.2021; 1865(3): 129834.     CrossRef
  • The Influence of Obesity and Associated Fatty Acids on Placental Inflammation
    Alison J. Eastman, Rebecca E. Moore, Steven D. Townsend, Jennifer A. Gaddy, David M. Aronoff
    Clinical Therapeutics.2021; 43(2): 265.     CrossRef
  • Targeting the G protein-coupled estrogen receptor (GPER) in obesity and diabetes
    Geetanjali Sharma, Eric R. Prossnitz
    Endocrine and Metabolic Science.2021; 2: 100080.     CrossRef
  • Changes in Body Composition Are Associated with Metabolic Changes and the Risk of Metabolic Syndrome
    Yun Hwan Oh, Seulggie Choi, Gyeongsil Lee, Joung Sik Son, Kyae Hyung Kim, Sang Min Park
    Journal of Clinical Medicine.2021; 10(4): 745.     CrossRef
  • N6-Adenosine Methylation (m6A) RNA Modification: an Emerging Role in Cardiovascular Diseases
    Ye-shi Chen, Xin-ping Ouyang, Xiao-hua Yu, Petr Novák, Le Zhou, Ping-ping He, Kai Yin
    Journal of Cardiovascular Translational Research.2021; 14(5): 857.     CrossRef
  • From Metabolic Syndrome to Neurological Diseases: Role of Autophagy
    Jessica Maiuolo, Micaela Gliozzi, Vincenzo Musolino, Cristina Carresi, Federica Scarano, Saverio Nucera, Miriam Scicchitano, Francesca Bosco, Stefano Ruga, Maria Caterina Zito, Roberta Macri, Rosamaria Bulotta, Carolina Muscoli, Vincenzo Mollace
    Frontiers in Cell and Developmental Biology.2021;[Epub]     CrossRef
  • Absent Exercise-Induced Improvements in Fat Oxidation in Women With Polycystic Ovary Syndrome After High-Intensity Interval Training
    Sofie Lionett, Ida Almenning Kiel, Ragnhild Røsbjørgen, Stian Lydersen, Steen Larsen, Trine Moholdt
    Frontiers in Physiology.2021;[Epub]     CrossRef
  • Roles of interstitial fluid pH and weak organic acids in development and amelioration of insulin resistance
    Yoshinori Marunaka
    Biochemical Society Transactions.2021; 49(2): 715.     CrossRef
  • The Role of Mitochondrial Adaptation and Metabolic Flexibility in the Pathophysiology of Obesity and Insulin Resistance: an Updated Overview
    Dimitrios Tsilingiris, Evangelia Tzeravini, Chrysi Koliaki, Maria Dalamaga, Alexander Kokkinos
    Current Obesity Reports.2021; 10(3): 191.     CrossRef
  • Obesity-Related Inflammation and Endothelial Dysfunction in COVID-19: Impact on Disease Severity
    Andrea De Lorenzo, Vanessa Estato, Hugo C Castro-Faria-Neto, Eduardo Tibirica
    Journal of Inflammation Research.2021; Volume 14: 2267.     CrossRef
  • Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential
    Bruna B. Brandão, Ankita Poojari, Atefeh Rabiee
    International Journal of Molecular Sciences.2021; 22(11): 5906.     CrossRef
  • Metabolic Syndrome in an Aging Society – Role of Oxidant-Antioxidant Imbalance and Inflammation Markers in Disentangling Atherosclerosis
    Sylwia Dziegielewska-Gesiak
    Clinical Interventions in Aging.2021; Volume 16: 1057.     CrossRef
  • Recruitment and remodeling of peridroplet mitochondria in human adipose tissue
    Rebeca Acín-Perez, Anton Petcherski, Michaela Veliova, Ilan Y. Benador, Essam A. Assali, Georgia Colleluori, Saverio Cinti, Alexandra J. Brownstein, Siyouneh Baghdasarian, Masha J. Livhits, Michael W. Yeh, Karthickeyan Chella Krishnan, Laurent Vergnes, Na
    Redox Biology.2021; 46: 102087.     CrossRef
  • New Insights Into Mitochondrial Dysfunction at Disease Susceptibility Loci in the Development of Type 2 Diabetes
    Hannah Maude, Winston Lau, Nikolas Maniatis, Toby Andrew
    Frontiers in Endocrinology.2021;[Epub]     CrossRef
  • Effects of sleeve gastrectomy on bone mass, microstructure of femurs and bone metabolism associated serum factors in obese rats
    Ying Xue, Ran Li, Yong Zhao, Ling Li, Yun Zhou
    BMC Endocrine Disorders.2021;[Epub]     CrossRef
  • The cyclin dependent kinase inhibitor Roscovitine prevents diet-induced metabolic disruption in obese mice
    Nabil Rabhi, Kathleen Desevin, Briana Noel Cortez, Ryan Hekman, Jean Z. Lin, Andrew Emili, Stephen R. Farmer
    Scientific Reports.2021;[Epub]     CrossRef
  • Reliability and variation in mitochondrial respiration in human adipose tissue
    Ronni Eg Sahl, Eva Frederikke Høy Helms, Malte Schmücker, Mathias Flensted-Jensen, Arthur Ingersen, Thomas Morville, Flemming Dela, Jørn Wulff Helge, Steen Larsen
    Adipocyte.2021; 10(1): 605.     CrossRef
  • Inhibition of protein tyrosine phosphatase improves mitochondrial bioenergetics and dynamics, reduces oxidative stress, and enhances adipogenic differentiation potential in metabolically impaired progenitor stem cells
    Katarzyna Kornicka-Garbowska, Lynda Bourebaba, Michael Röcken, Krzysztof Marycz
    Cell Communication and Signaling.2021;[Epub]     CrossRef
  • microRNAs in Human Adipose Tissue Physiology and Dysfunction
    Alina Kurylowicz
    Cells.2021; 10(12): 3342.     CrossRef
  • Aging, obese-insulin resistance, and bone remodeling
    Napatsorn Imerb, Chanisa Thonusin, Nipon Chattipakorn, Siriporn C. Chattipakorn
    Mechanisms of Ageing and Development.2020; 191: 111335.     CrossRef
  • Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes
    Federica Zatterale, Michele Longo, Jamal Naderi, Gregory Alexander Raciti, Antonella Desiderio, Claudia Miele, Francesco Beguinot
    Frontiers in Physiology.2020;[Epub]     CrossRef
  • Is Mitochondrial Dysfunction a Common Root of Noncommunicable Chronic Diseases?
    Alexis Diaz-Vegas, Pablo Sanchez-Aguilera, James R Krycer, Pablo E Morales, Matías Monsalves-Alvarez, Mariana Cifuentes, Beverly A Rothermel, Sergio Lavandero
    Endocrine Reviews.2020;[Epub]     CrossRef
  • Inflammatory Signaling and Brown Fat Activity
    Farah Omran, Mark Christian
    Frontiers in Endocrinology.2020;[Epub]     CrossRef
  • Omega-3 fatty acids as regulators of brown/beige adipose tissue: from mechanisms to therapeutic potential
    Marta Fernández-Galilea, Elisa Félix-Soriano, Ignacio Colón-Mesa, Xavier Escoté, Maria J. Moreno-Aliaga
    Journal of Physiology and Biochemistry.2020; 76(2): 251.     CrossRef
  • Anti-Inflammatory Strategies Targeting Metaflammation in Type 2 Diabetes
    Alina Kuryłowicz, Krzysztof Koźniewski
    Molecules.2020; 25(9): 2224.     CrossRef
  • Obese Adipose Tissue Secretion Induces Inflammation in Preadipocytes: Role of Toll-Like Receptor-4
    Mariana Renovato-Martins, Catharina Moreira-Nunes, Georgia C. Atella, Christina Barja-Fidalgo, João Alfredo de Moraes
    Nutrients.2020; 12(9): 2828.     CrossRef
  • Diabetes and Metabolism Journal in 2020: Good to Great
    In-Kyung Jeong
    Diabetes & Metabolism Journal.2020; 44(1): 1.     CrossRef
  • The Effect of Silibinin on Protein Expression Profile in White Adipose Tissue of Obese Mice
    Fei Wang, Shuchun Chen, Luping Ren, Yichao Wang, Zelin Li, Tiantian Song, He Zhang, Qiwen Yang
    Frontiers in Pharmacology.2020;[Epub]     CrossRef
  • Beneficial Effects of Bariatric Surgery-Induced by Weight Loss on the Proteome of Abdominal Subcutaneous Adipose Tissue
    Bárbara María Varela-Rodríguez, Paula Juiz-Valiña, Luis Varela, Elena Outeiriño-Blanco, Susana Belén Bravo, María Jesús García-Brao, Enrique Mena, José Francisco Noguera, Javier Valero-Gasalla, Fernando Cordido, Susana Sangiao-Alvarellos
    Journal of Clinical Medicine.2020; 9(1): 213.     CrossRef
  • Impact of Skeletal Muscle Mass on Metabolic Health
    Gyuri Kim, Jae Hyeon Kim
    Endocrinology and Metabolism.2020; 35(1): 1.     CrossRef
  • Sea buckthorn (Hippophae rhamnoides L.) oil enhances proliferation, adipocytes differentiation and insulin sensitivity in 3T3-L1 cells
    Ting Zhang, Xuze Qin, Yuxin Cao, Jianxin Zhang, Junxing Zhao
    Food Science and Biotechnology.2020; 29(11): 1511.     CrossRef
  • Adipose tissue secretory profile and cardiometabolic risk in obesity
    Pengcheng Zhang, Daniels Konja, Yu Wang
    Endocrine and Metabolic Science.2020; 1(3-4): 100061.     CrossRef
  • Mitochondrial Dynamics in the Brain Are Associated With Feeding, Glucose Homeostasis, and Whole-Body Metabolism
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Review
Obesity and Metabolic Syndrome
Role of the Pyruvate Dehydrogenase Complex in Metabolic Remodeling: Differential Pyruvate Dehydrogenase Complex Functions in Metabolism
Sungmi Park, Jae-Han Jeon, Byong-Keol Min, Chae-Myeong Ha, Themis Thoudam, Bo-Yoon Park, In-Kyu Lee
Diabetes Metab J. 2018;42(4):270-281.   Published online August 21, 2018
DOI: https://doi.org/10.4093/dmj.2018.0101
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AbstractAbstract PDFPubReader   

Mitochondrial dysfunction is a hallmark of metabolic diseases such as obesity, type 2 diabetes mellitus, neurodegenerative diseases, and cancers. Dysfunction occurs in part because of altered regulation of the mitochondrial pyruvate dehydrogenase complex (PDC), which acts as a central metabolic node that mediates pyruvate oxidation after glycolysis and fuels the Krebs cycle to meet energy demands. Fine-tuning of PDC activity has been mainly attributed to post-translational modifications of its subunits, including the extensively studied phosphorylation and de-phosphorylation of the E1α subunit of pyruvate dehydrogenase (PDH), modulated by kinases (pyruvate dehydrogenase kinase [PDK] 1-4) and phosphatases (pyruvate dehydrogenase phosphatase [PDP] 1-2), respectively. In addition to phosphorylation, other covalent modifications, including acetylation and succinylation, and changes in metabolite levels via metabolic pathways linked to utilization of glucose, fatty acids, and amino acids, have been identified. In this review, we will summarize the roles of PDC in diverse tissues and how regulation of its activity is affected in various metabolic disorders.

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  • Mitochondria dysfunction induced by decyl-TPP mitochondriotropic antioxidant based on caffeic acid AntiOxCIN6 sensitizes cisplatin lung anticancer therapy due to a remodeling of energy metabolism
    Ricardo Amorim, Carina C. Magalhães, Sofia Benfeito, Fernando Cagide, Ludgero C. Tavares, Katia Santos, Vilma A. Sardão, Sandipan Datta, Gino A. Cortopassi, Inês Baldeiras, John G. Jones, Fernanda Borges, Paulo J. Oliveira, José Teixeira
    Biochemical Pharmacology.2024; 219: 115953.     CrossRef
  • Thiamine analogues featuring amino-oxetanes as potent and selective inhibitors of pyruvate dehydrogenase
    Alex H.Y. Chan, Terence C.S. Ho, Finian J. Leeper
    Bioorganic & Medicinal Chemistry Letters.2024; 98: 129571.     CrossRef
  • Pyruvate Dehydrogenase Complex in Neonatal Hypoxic–Ischemic Brain Injury
    Tao Zhou, Yuangao Zhong, Yong Zhang, Yue Zhou
    ACS Pharmacology & Translational Science.2024; 7(1): 42.     CrossRef
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    Kuo Chi, Jing Liu, Xinghua Li, He Wang, Yanliang Li, Qingnan Liu, Yabin Zhou, Yuan Ge
    Molecular Omics.2024; 20(3): 169.     CrossRef
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    Hongce Song, Chaoyi Xie, Meiyun Dong, Yuxuan Zhang, Haifeng Huang, Yijing Han, Yaqiong Liu, Lei Wei, Xiaotong Wang
    Ecotoxicology and Environmental Safety.2024; 274: 116236.     CrossRef
  • Autocrine phosphatase PDP2 inhibits ferroptosis by dephosphorylating ACSL4 in the Luminal A Breast Cancer
    Jun-Jie Zhu, Feng-Ying Huang, Hengyu Chen, Yun-long Zhang, Ming-Hui Chen, Ri-Hong Wu, Shu-Zhen Dai, Gui-Sheng He, Guang-Hong Tan, Wu-Ping Zheng, Sreeparna Banerjee
    PLOS ONE.2024; 19(3): e0299571.     CrossRef
  • Glutaminase potentiates the glycolysis in esophageal squamous cell carcinoma by interacting with PDK1
    Guangzhao Zhu, Fangxia Guan, Shenglei Li, Qing Zhang, Xueying Zhang, Yue Qin, Zhangzhan Sun, Shaohua Peng, Jiexing Cheng, Yiyang Li, Ruili Ren, Tianli Fan, Hongtao Liu
    Molecular Carcinogenesis.2024; 63(5): 897.     CrossRef
  • Inhibition of Pyruvate Dehydrogenase Kinase 4 in CD4+ T Cells Ameliorates Intestinal Inflammation
    Hoyul Lee, Jae Han Jeon, Yu-Jeong Lee, Mi-Jin Kim, Woong Hee Kwon, Dipanjan Chanda, Themis Thoudam, Haushabhau S. Pagire, Suvarna H. Pagire, Jin Hee Ahn, Robert A. Harris, Eun Soo Kim, In-Kyu Lee
    Cellular and Molecular Gastroenterology and Hepatology.2023; 15(2): 439.     CrossRef
  • Nitric oxide regulation of cellular metabolism: Adaptive tuning of cellular energy
    Gregory Pappas, Melissa L. Wilkinson, Andrew J. Gow
    Nitric Oxide.2023; 131: 8.     CrossRef
  • Furan-based inhibitors of pyruvate dehydrogenase: SAR study, biochemical evaluation and computational analysis
    Alex H. Y. Chan, Terence C. S. Ho, Daniel R. Parle, Finian J. Leeper
    Organic & Biomolecular Chemistry.2023; 21(8): 1755.     CrossRef
  • The pyruvate dehydrogenase complex: Life’s essential, vulnerable and druggable energy homeostat
    Peter W. Stacpoole, Charles E. McCall
    Mitochondrion.2023; 70: 59.     CrossRef
  • The Impact of Krebs Cycle Intermediates on the Endocrine System and Immune System: A Comparison
    Borros M. Arneth
    Endocrines.2023; 4(1): 179.     CrossRef
  • Consequences of reprogramming acetyl-CoA metabolism by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse liver
    Giovan N. Cholico, Karina Orlowska, Russell R. Fling, Warren J. Sink, Nicholas A. Zacharewski, Kelly A. Fader, Rance Nault, Tim Zacharewski
    Scientific Reports.2023;[Epub]     CrossRef
  • The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4
    Min-Ji Kim, Ibotombi Singh Sinam, Zerwa Siddique, Jae-Han Jeon, In-Kyu Lee
    Diabetes & Metabolism Journal.2023; 47(2): 153.     CrossRef
  • Targeting PDK2 rescues stress-induced impaired brain energy metabolism
    Changshui Wang, Changmeng Cui, Pengfei Xu, Li Zhu, Hongjia Xue, Beibei Chen, Pei Jiang
    Molecular Psychiatry.2023; 28(10): 4138.     CrossRef
  • The Role of Pyruvate Metabolism in Mitochondrial Quality Control and Inflammation
    Min-Ji Kim, Hoyul Lee, Dipanjan Chanda, Themis Thoudam, Hyeon-Ji Kang, Robert A. Harris, In-Kyu Lee
    Molecules and Cells.2023; 46(5): 259.     CrossRef
  • Inhibition of pyruvate dehydrogenase kinase 4 ameliorates kidney ischemia-reperfusion injury by reducing succinate accumulation during ischemia and preserving mitochondrial function during reperfusion
    Chang Joo Oh, Min-Ji Kim, Ji-Min Lee, Dong Hun Kim, Il-Young Kim, Sanghee Park, Yeongmin Kim, Kyung-Bok Lee, Sang-Hee Lee, Chae Won Lim, Myeongjin Kim, Jung-Yi Lee, Haushabhau S. Pagire, Suvarna H. Pagire, Myung Ae Bae, Dipanjan Chanda, Themis Thoudam, Ah
    Kidney International.2023; 104(4): 724.     CrossRef
  • PDHA1 hyperacetylation-mediated lactate overproduction promotes sepsis-induced acute kidney injury via Fis1 lactylation
    Sheng An, Yi Yao, Hongbin Hu, Junjie Wu, Jiaxin Li, Lulan Li, Jie Wu, Maomao Sun, Zhiya Deng, Yaoyuan Zhang, Shenhai Gong, Qiaobing Huang, Zhongqing Chen, Zhenhua Zeng
    Cell Death & Disease.2023;[Epub]     CrossRef
  • Iron promotes glycolysis to drive colon tumorigenesis
    Zhaoli Liu, Luke Villareal, Lavanya Goodla, Hyeoncheol Kim, Daniel M. Falcon, Mohammad Haneef, David R. Martin, Li Zhang, Ho-Joon Lee, Daniel Kremer, Costas A. Lyssiotis, Yatrik M. Shah, Henry C. Lin, Hui-kuan Lin, Xiang Xue
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2023; 1869(8): 166846.     CrossRef
  • Driving force of deteriorated cellular environment in heart failure: Metabolic remodeling
    Lu Fan, Chenchen Meng, Xiaoming Wang, Yunjiao Wang, Yanyang Li, Shichao Lv, Junping Zhang
    Clinics.2023; 78: 100263.     CrossRef
  • Mitochondrial dysfunctions in T cells: focus on inflammatory bowel disease
    Hoyul Lee, Jae-Han Jeon, Eun Soo Kim
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Adrenomedullin induces cisplatin chemoresistance in ovarian cancer through reprogramming of glucose metabolism
    Lei Dou, Enting Lu, Dongli Tian, Fangmei Li, Lei Deng, Yi Zhang
    Journal of Translational Internal Medicine.2023; 11(2): 169.     CrossRef
  • Metabolic deregulation associated with aging modulates protein aggregation in the yeast model of Huntington’s disease
    Sai Sanwid Pradhan, Sai Swaroop R., Sai Phalguna Kanikaram, Datta Darshan V.M., Ashish Pargaonkar, Rajesh Babu Dandamudi, Venketesh Sivaramakrishnan
    Journal of Biomolecular Structure and Dynamics.2023; : 1.     CrossRef
  • Unique and generic crossed metabolism in response to four sub-lethal environmental stresses in the oriental fruit fly, Bactrocera dorsalis Hendel
    Lili Ren, Hongxia Zhang, Jiao Zhou, Yajing Wu, Bo Liu, Shuping Wang, Xin Liu, Xin Hao, Lilin Zhao
    Ecotoxicology and Environmental Safety.2023; 264: 115434.     CrossRef
  • Oxidative stress regulation and related metabolic pathways in epithelial–mesenchymal transition of breast cancer stem cells
    Raheleh Farahzadi, Behnaz Valipour, Ezzatollah Fathi, Samaneh Pirmoradi, Ommoleila Molavi, Soheila Montazersaheb, Zohreh Sanaat
    Stem Cell Research & Therapy.2023;[Epub]     CrossRef
  • Preclinical Study in Mouse Thymus and Thymocytes: Effects of Treatment with a Combination of Sodium Dichloroacetate and Sodium Valproate on Infectious Inflammation Pathways
    Donatas Stakišaitis, Linas Kapočius, Evelina Kilimaitė, Dovydas Gečys, Lina Šlekienė, Ingrida Balnytė, Jolita Palubinskienė, Vaiva Lesauskaitė
    Pharmaceutics.2023; 15(12): 2715.     CrossRef
  • Contrasting effects of whole-body and hepatocyte-specific deletion of the RNA polymerase III repressor Maf1 in the mouse
    Gilles Willemin, François Mange, Viviane Praz, Séverine Lorrain, Pascal Cousin, Catherine Roger, Ian M. Willis, Nouria Hernandez
    Frontiers in Molecular Biosciences.2023;[Epub]     CrossRef
  • Reprogramming of glucose metabolism of cumulus cells and oocytes and its therapeutic significance
    Shogo Imanaka, Hiroshi Shigetomi, Hiroshi Kobayashi
    Reproductive Sciences.2022; 29(3): 653.     CrossRef
  • Renal denervation ameliorates cardiac metabolic remodeling in diabetic cardiomyopathy rats by suppressing renal SGLT2 expression
    Jun-Yu Huo, Wan-Ying Jiang, Shi-Geng Zhang, Yi-Ting Lyu, Jie Geng, Meng Chen, Yuan-Yuan Chen, Zhi-Xin Jiang, Qi-Jun Shan
    Laboratory Investigation.2022; 102(4): 341.     CrossRef
  • Alteration in glycolytic/cholesterogenic gene expression is associated with bladder cancer prognosis and immune cell infiltration
    Yuying Zhang, Baoyi Zhu, Yi Cai, Sihua Zhu, Hongjun Zhao, Xiaoling Ying, Chonghe Jiang, Jianwen Zeng
    BMC Cancer.2022;[Epub]     CrossRef
  • Protein phosphorylation in hemocytes of Fenneropenaeus chinensis in response to white spot syndrome virus infection
    Xiaoqian Tang, Ting Liu, Xiaoai Li, Xiuzhen Sheng, Jing Xing, Heng Chi, Wenbin Zhan
    Fish & Shellfish Immunology.2022; 122: 106.     CrossRef
  • The Critical Role Played by Mitochondrial MITF Serine 73 Phosphorylation in Immunologically Activated Mast Cells
    Lakshmi Bhargavi Paruchuru, Sharmila Govindaraj, Ehud Razin
    Cells.2022; 11(3): 589.     CrossRef
  • Glycemic Control and the Heart: The Tale of Diabetic Cardiomyopathy Continues
    Miriam Longo, Lorenzo Scappaticcio, Paolo Cirillo, Antonietta Maio, Raffaela Carotenuto, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
    Biomolecules.2022; 12(2): 272.     CrossRef
  • Metabolic Reprogramming in Response to Alterations of Mitochondrial DNA and Mitochondrial Dysfunction in Gastric Adenocarcinoma
    Tzu-Ching Chang, Hui-Ting Lee, Siao-Cian Pan, Shih-Han Cho, Chieh Cheng, Liang-Hung Ou, Chia-I Lin, Chen-Sung Lin, Yau-Huei Wei
    International Journal of Molecular Sciences.2022; 23(3): 1857.     CrossRef
  • Toxicological effects of tris(1,3-dichloro-2-propyl) phosphate in oyster Crassostrea gigas using proteomic and phosphoproteomic analyses
    Chengcheng Yin, Zuodeng Sun, Chenglong Ji, Fei Li, Huifeng Wu
    Journal of Hazardous Materials.2022; 434: 128824.     CrossRef
  • Water-Extracted Prunella vulgaris Alleviates Endometriosis by Reducing Aerobic Glycolysis
    Min Kyoung Cho, Ling Jin, Jung Ho Han, Jung-Suk Jin, Se-Yun Cheon, Su Shin, Sung-Jin Bae, Jang-Kyung Park, Ki-Tae Ha
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Pyruvate Dehydrogenase A1 Phosphorylated by Insulin Associates with Pyruvate Kinase M2 and Induces LINC00273 through Histone Acetylation
    Abu Jubayer Hossain, Rokibul Islam, Jae-Gyu Kim, Oyungerel Dogsom, Kim Cuong Cap, Jae-Bong Park
    Biomedicines.2022; 10(6): 1256.     CrossRef
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    Mohamad Hafizi Abu Bakar, Nor Shafiqah Nor Shahril, Mohamad Shamil Faris Mohamad Khalid, Sharifah Mohammad, Khairul Anuar Shariff, Thiruventhan Karunakaran, Rabeta Mohd Salleh, Mohamad Norisham Mohamad Rosdi
    Toxicology and Applied Pharmacology.2022; 449: 116099.     CrossRef
  • Regulation of Metabolism by Mitochondrial MUL1 E3 Ubiquitin Ligase
    Lucia Cilenti, Rohit Mahar, Jacopo Di Gregorio, Camilla T. Ambivero, Matthew E. Merritt, Antonis S. Zervos
    Frontiers in Cell and Developmental Biology.2022;[Epub]     CrossRef
  • The Pyruvate Dehydrogenase Complex Mitigates LPS-Induced Endothelial Barrier Dysfunction by Metabolic Regulation
    Liangfeng Mao, Maomao Sun, Zhenfeng Chen, Zhenhua Zeng, Jie Wu, Zhongqing Chen, Weijin Zhang, Qiaobing Huang
    Shock.2022; 57(6): 308.     CrossRef
  • Review: Influence of postabsorptive metabolism on essential amino acid partitioning in lactating dairy cows
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    animal.2022; 16: 100573.     CrossRef
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    Chung-Hsing Wang, Wen-Li Lu, Shang-Lun Chiang, Tsung-Hsun Tsai, Su-Ching Liu, Chia-Hung Hsieh, Pen-Hua Su, Chih-Yang Huang, Fuu-Jen Tsai, Yu-Jung Lin, Yu-Nan Huang
    The Journal of Clinical Endocrinology & Metabolism.2022; 107(9): 2556.     CrossRef
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    Molecules and Cells.2022; 45(7): 454.     CrossRef
  • Metabolic regulation of T cell development
    Mengdi Zhang, Xiaoxi Lin, Zhou Yang, Xia Li, Zhiguang Zhou, Paul E. Love, Jiaqi Huang, Bin Zhao
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • Noncanonical PDK4 action alters mitochondrial dynamics to affect the cellular respiratory status
    Themis Thoudam, Dipanjan Chanda, Ibotombi Singh Sinam, Byung-Gyu Kim, Mi-Jin Kim, Chang Joo Oh, Jung Yi Lee, Min-Ji Kim, Soo Yeun Park, Shin Yup Lee, Min-Kyo Jung, Ji Young Mun, Robert A. Harris, Naotada Ishihara, Jae-Han Jeon, In-Kyu Lee
    Proceedings of the National Academy of Sciences.2022;[Epub]     CrossRef
  • Frontiers in the enzymology of thiamin diphosphate-dependent enzymes
    Sabin Prajapati, Fabian Rabe von Pappenheim, Kai Tittmann
    Current Opinion in Structural Biology.2022; 76: 102441.     CrossRef
  • The Role of the Pyruvate Dehydrogenase Complex in the Development of Ischemic-Reperfusion Syndrome
    K. A. Popov, Ya. E. Denisova, I. M. Bykov, I. Yu. Tsymbalyuk, G. A. Ermakova, A. G. Zavgorodnyaya, A. S. Shevchenko
    Kuban Scientific Medical Bulletin.2022; 29(4): 75.     CrossRef
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    International Journal of Biological Macromolecules.2022; 221: 83.     CrossRef
  • Distinct role of mitochondrial function and protein kinase C in intimal and medial calcification in vitro
    Marina A. Heuschkel, Anne Babler, Jonas Heyn, Emiel P. C. van der Vorst, Marja Steenman, Maren Gesper, Ben A. Kappel, David Magne, Yann Gouëffic, Rafael Kramann, Willi Jahnen-Dechent, Nikolaus Marx, Thibaut Quillard, Claudia Goettsch
    Frontiers in Cardiovascular Medicine.2022;[Epub]     CrossRef
  • Metabolomic responses in livers of female and male zebrafish (Danio rerio) following prolonged exposure to environmental levels of zinc oxide nanoparticles
    Xiaohong Wang, Siying Chen, Yingju Qin, Haiqing Wang, Zhenda Liang, Yuanhui Zhao, Li Zhou, Christopher J. Martyniuk
    Aquatic Toxicology.2022; 253: 106333.     CrossRef
  • A Missense Variant in PDK1 Associated with Severe Neurodevelopmental Delay and Epilepsy
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    Biomedicines.2022; 10(12): 3171.     CrossRef
  • Rg3 regulates myocardial pyruvate metabolism via P300-mediated dihydrolipoamide dehydrogenase 2-hydroxyisobutyrylation in TAC-induced cardiac hypertrophy
    Jingyu Ni, Hao Zhang, Xiaodan Wang, Zhihao Liu, Tong Nie, Lan Li, Jing Su, Yan Zhu, Chuanrui Ma, Yuting Huang, Jingyuan Mao, Xiumei Gao, Guanwei Fan
    Cell Death & Disease.2022;[Epub]     CrossRef
  • Glutamine mitigates murine burn sepsis by supporting macrophage M2 polarization through repressing the SIRT5-mediated desuccinylation of pyruvate dehydrogenase
    Yuanfeng Zhu, Xiaoli Chen, Yongling Lu, Lin Xia, Shijun Fan, Qianying Huang, Xin Liu, Xi Peng
    Burns & Trauma.2022;[Epub]     CrossRef
  • Loss of metabolic flexibility as a result of overexpression of pyruvate dehydrogenase kinases in muscle, liver and the immune system: Therapeutic targets in metabolic diseases
    Jae‐Han Jeon, Themis Thoudam, Eun Jung Choi, Min‐Ji Kim, Robert A Harris, In‐Kyu Lee
    Journal of Diabetes Investigation.2021; 12(1): 21.     CrossRef
  • Insulin resistance is mechanistically linked to hepatic mitochondrial remodeling in non-alcoholic fatty liver disease
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    Molecular Metabolism.2021; 45: 101154.     CrossRef
  • Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases
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    International Journal of Molecular Sciences.2021; 22(2): 764.     CrossRef
  • Hyperpolarized magnetic resonance shows that the anti‐ischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved post‐ischemic function in the diabetic heart
    Dragana Savic, Vicky Ball, Lorenz Holzner, David Hauton, Kerstin N. Timm, M. Kate Curtis, Lisa C. Heather, Damian J. Tyler
    NMR in Biomedicine.2021;[Epub]     CrossRef
  • Beyond the Warburg Effect: Oxidative and Glycolytic Phenotypes Coexist within the Metabolic Heterogeneity of Glioblastoma
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    Cells.2021; 10(2): 202.     CrossRef
  • Detailed evaluation of pyruvate dehydrogenase complex inhibition in simulated exercise conditions
    Bodhi A. Jelinek, Michael A. Moxley
    Biophysical Journal.2021; 120(5): 936.     CrossRef
  • Proteomics Approach of Rapamycin Anti-Tumoral Effect on Primary and Metastatic Canine Mammary Tumor Cells In Vitro
    Patrícia F. Lainetti, Antonio F. Leis-Filho, Priscila E. Kobayashi, Laíza S. de Camargo, Renee Laufer-Amorim, Carlos E. Fonseca-Alves, Fabiana F. Souza
    Molecules.2021; 26(5): 1213.     CrossRef
  • Remodeling of Cancer-Specific Metabolism under Hypoxia with Lactate Calcium Salt in Human Colorectal Cancer Cells
    Keun-Yeong Jeong, Jae-Jun Sim, Min Hee Park, Hwan Mook Kim
    Cancers.2021; 13(7): 1518.     CrossRef
  • The Metabolic Fates of Pyruvate in Normal and Neoplastic Cells
    Edward V. Prochownik, Huabo Wang
    Cells.2021; 10(4): 762.     CrossRef
  • The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction
    Hilary Y. Liu, Jenna R. Gale, Ian J. Reynolds, John H. Weiss, Elias Aizenman
    Biomedicines.2021; 9(5): 489.     CrossRef
  • Melatonin inhibits lung cancer development by reversing the Warburg effect via stimulating the SIRT3/PDH axis
    Xiangyun Chen, Bingjie Hao, Dan Li, Russel J. Reiter, Yidong Bai, Baigenzhin Abay, Guojie Chen, Shumeng Lin, Tiansheng Zheng, Yanbei Ren, Xiao Xu, Ming Li, Lihong Fan
    Journal of Pineal Research.2021;[Epub]     CrossRef
  • Differential expression of pyruvate dehydrogenase E1A and its inactive phosphorylated form among breast cancer subtypes
    Dana M. Zaher, Iman M. Talaat, Amal Hussein, Mahmood Y. Hachim, Hany A. Omar
    Life Sciences.2021; 284: 119885.     CrossRef
  • Structure of the native pyruvate dehydrogenase complex reveals the mechanism of substrate insertion
    Jana Škerlová, Jens Berndtsson, Hendrik Nolte, Martin Ott, Pål Stenmark
    Nature Communications.2021;[Epub]     CrossRef
  • Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders
    Doris Loh, Russel J. Reiter
    Antioxidants.2021; 10(9): 1483.     CrossRef
  • Comprehensive Interrogation of Metabolic and Bioenergetic Responses of Early-Staged Zebrafish (Danio rerio) to a Commercial Copper Hydroxide Nanopesticide
    Xiaohong Wang, Yingju Qin, Xiaoyu Li, Bing Yan, Christopher J. Martyniuk
    Environmental Science & Technology.2021;[Epub]     CrossRef
  • Conditional Knockout of Pdha1 in Mouse Hippocampus Impairs Cognitive Function: The Possible Involvement of Lactate
    Wanxin Chen, Xiaoxia Sun, Libin Zhan, Wen Zhou, Tingting Bi
    Frontiers in Neuroscience.2021;[Epub]     CrossRef
  • Dihydrolipoamide dehydrogenase, pyruvate oxidation, and acetylation-dependent mechanisms intersecting drug iatrogenesis
    I. F. Duarte, J. Caio, M. F. Moedas, L. A. Rodrigues, A. P. Leandro, I. A. Rivera, M. F. B. Silva
    Cellular and Molecular Life Sciences.2021; 78(23): 7451.     CrossRef
  • Advanced Bioinformatics Tools in the Pharmacokinetic Profiles of Natural and Synthetic Compounds with Anti-Diabetic Activity
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    Biomolecules.2021; 11(11): 1692.     CrossRef
  • Obesidade e infecção por SARS-CoV-2: papel da metainflamação
    Ana Luísa Silva Albertoni, Luis Gustavo Silva Albertoni, Patricia Elaine de Almeida
    HU Revista.2021; 46: 1.     CrossRef
  • Influenza and obesity: its odd relationship and the lessons for COVID-19 pandemic
    Livio Luzi, Maria Grazia Radaelli
    Acta Diabetologica.2020; 57(6): 759.     CrossRef
  • Acquisition of exogenous fatty acids renders apicoplast-based biosynthesis dispensable in tachyzoites of Toxoplasma
    Xiaohan Liang, Jianmin Cui, Xuke Yang, Ningbo Xia, Yaqiong Li, Junlong Zhao, Nishith Gupta, Bang Shen
    Journal of Biological Chemistry.2020; 295(22): 7743.     CrossRef
  • Stimulation of glycolysis promotes cardiomyocyte proliferation after injury in adult zebrafish
    Ryuichi Fukuda, Rubén Marín‐Juez, Hadil El‐Sammak, Arica Beisaw, Radhan Ramadass, Carsten Kuenne, Stefan Guenther, Anne Konzer, Aditya M Bhagwat, Johannes Graumann, Didier YR Stainier
    EMBO reports.2020;[Epub]     CrossRef
  • Fat mass affects nutritional status of ICU COVID-19 patients
    Antonino De Lorenzo, Maria Grazia Tarsitano, Carmela Falcone, Laura Di Renzo, Lorenzo Romano, Sebastiano Macheda, Anna Ferrarelli, Demetrio Labate, Marco Tescione, Federico Bilotta, Paola Gualtieri
    Journal of Translational Medicine.2020;[Epub]     CrossRef
  • Conditional knockout of pyruvate dehydrogenase in mouse pancreatic β‑cells causes morphological and functional changes
    Xiao Wang, Shuchang Lai, Yanshi Ye, Yuanyuan Hu, Daoyan Pan, Xiaochun Bai, Jie Shen
    Molecular Medicine Reports.2020;[Epub]     CrossRef
  • Beneficial Effects of Acetyl-DL-Leucine (ADLL) in a Mouse Model of Sandhoff Disease
    Ecem Kaya, David A. Smith, Claire Smith, Barry Boland, Michael Strupp, Frances M. Platt
    Journal of Clinical Medicine.2020; 9(4): 1050.     CrossRef
  • Fetal circulating human resistin increases in diabetes during pregnancy and impairs placental mitochondrial biogenesis
    Shaoning Jiang, April M. Teague, Jeanie B. Tryggestad, Timothy J. Lyons, Steven D. Chernausek
    Molecular Medicine.2020;[Epub]     CrossRef
  • SARS-CoV-2-host dynamics: Increased risk of adverse outcomes of COVID-19 in obesity
    Rakhee Yadav, Sandeep Aggarwal, Archna Singh
    Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2020; 14(5): 1355.     CrossRef
  • Effect of flaxseed oil on muscle protein loss and carbohydrate oxidation impairment in a pig model after lipopolysaccharide challenge
    Ping Kang, Yang Wang, Xiangen Li, Zhicheng Wan, Xiuying Wang, Huiling Zhu, Chunwei Wang, Shengjun Zhao, Huifu Chen, Yulan Liu
    British Journal of Nutrition.2020; 123(8): 859.     CrossRef
  • Arrangement and symmetry of the fungal E3BP-containing core of the pyruvate dehydrogenase complex
    B. O. Forsberg, S. Aibara, R. J. Howard, N. Mortezaei, E. Lindahl
    Nature Communications.2020;[Epub]     CrossRef
  • The potential impacts of obesity on COVID-19
    Ahmed Abdalazim Dafallah Albashir
    Clinical Medicine.2020; 20(4): e109.     CrossRef
  • Selective dietary polyphenols induce differentiation of human osteoblasts by adiponectin receptor 1-mediated reprogramming of mitochondrial energy metabolism
    Subhashis Pal, Konica Porwal, Sangam Rajak, Rohit A. Sinha, Naibedya Chattopadhyay
    Biomedicine & Pharmacotherapy.2020; 127: 110207.     CrossRef
  • Factors Associated with Increased Morbidity and Mortality of Obese and Overweight COVID-19 Patients
    Amany Magdy Beshbishy, Helal F. Hetta, Diaa E. Hussein, Abdullah A. Saati, Christian C. Uba, Nallely Rivero-Perez, Adrian Zaragoza-Bastida, Muhammad Ajmal Shah, Tapan Behl, Gaber El-Saber Batiha
    Biology.2020; 9(9): 280.     CrossRef
  • Increased Glucose Availability Attenuates Myocardial Ketone Body Utilization
    Manoja K. Brahma, Chae‐Myeong Ha, Mark E. Pepin, Sobuj Mia, Zhihuan Sun, John C. Chatham, Kirk M. Habegger, Evan Dale Abel, Andrew J. Paterson, Martin E. Young, Adam R. Wende
    Journal of the American Heart Association.2020;[Epub]     CrossRef
  • Stimulating pyruvate dehydrogenase complex reduces itaconate levels and enhances TCA cycle anabolic bioenergetics in acutely inflamed monocytes
    Xuewei Zhu, David Long, Manal Zabalawi, Brian Ingram, Barbara K. Yoza, Peter W. Stacpoole, Charles E. McCall
    Journal of Leukocyte Biology.2020; 107(3): 467.     CrossRef
  • Short-term high-fat diet intake leads to exacerbation of concanavalin A-induced liver injury through the induction of procoagulation state
    Eri Nanizawa, Yuki Tamaki, Reika Sono, Rintaro Miyashita, Yumi Hayashi, Ayumu Kanbe, Hiroyasu Ito, Tetsuya Ishikawa
    Biochemistry and Biophysics Reports.2020; 22: 100736.     CrossRef
  • Role of the Mitochondrial Pyruvate Carrier in the Occurrence of Metabolic Inflexibility in Drosophila melanogaster Exposed to Dietary Sucrose
    Chloé J. Simard, Mohamed Touaibia, Eric Pierre Allain, Etienne Hebert-Chatelain, Nicolas Pichaud
    Metabolites.2020; 10(10): 411.     CrossRef
  • Metabolic shift underlies recovery in reversible infantile respiratory chain deficiency
    Denisa Hathazi, Helen Griffin, Matthew J Jennings, Michele Giunta, Christopher Powell, Sarah F Pearce, Benjamin Munro, Wei Wei, Veronika Boczonadi, Joanna Poulton, Angela Pyle, Claudia Calabrese, Aurora Gomez‐Duran, Ulrike Schara, Robert D S Pitceathly, M
    The EMBO Journal.2020;[Epub]     CrossRef
  • Increased pyruvate dehydrogenase activity in skeletal muscle of growth-restricted ovine fetuses
    Alexander L. Pendleton, Laurel R. Humphreys, Melissa A. Davis, Leticia E. Camacho, Miranda J. Anderson, Sean W. Limesand
    American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.2019; 317(4): R513.     CrossRef
  • Recent advances in the pathogenesis of microvascular complications in diabetes
    Sungmi Park, Hyeon-Ji Kang, Jae-Han Jeon, Min-Ji Kim, In-Kyu Lee
    Archives of Pharmacal Research.2019; 42(3): 252.     CrossRef
  • Secondary Metabolites of The Endophytic Fungus Alternaria alternata JS0515 Isolated from Vitex rotundifolia and Their Effects on Pyruvate Dehydrogenase activity
    Changyeol Lee, Wei Li, Sunghee Bang, Sun Joo Lee, Nam-young Kang, Soonok Kim, Tae In Kim, Younghoon Go, Sang Hee Shim
    Molecules.2019; 24(24): 4450.     CrossRef
  • Adaptations in Protein Expression and Regulated Activity of Pyruvate Dehydrogenase Multienzyme Complex in Human Systolic Heart Failure
    Freya L. Sheeran, Julie Angerosa, Norman Y. Liaw, Michael M. Cheung, Salvatore Pepe
    Oxidative Medicine and Cellular Longevity.2019; 2019: 1.     CrossRef
  • Progression of Multifaceted Immune Cells in Atherosclerotic Development
    Sungmi Park, In-Kyu Lee
    Journal of Lipid and Atherosclerosis.2019; 8(1): 15.     CrossRef
  • SIRT3 elicited an anti‐Warburg effect through HIF1α/PDK1/PDHA1 to inhibit cholangiocarcinoma tumorigenesis
    Lei Xu, Yang Li, Lixing Zhou, Robert Gregory Dorfman, Li Liu, Rui Cai, Chenfei Jiang, Dehua Tang, Yuming Wang, Xiaoping Zou, Lei Wang, Mingming Zhang
    Cancer Medicine.2019; 8(5): 2380.     CrossRef
  • Differential Mechanism of ATP Production Occurs in Response to Succinylacetone in Colon Cancer Cells
    Lee, Woo, Yoo, Cho, Kim
    Molecules.2019; 24(19): 3575.     CrossRef
  • Myocardial Adaptation in Pseudohypoxia: Signaling and Regulation of mPTP via Mitochondrial Connexin 43 and Cardiolipin
    Miroslav Ferko, Natália Andelová, Barbara Szeiffová Bačová, Magdaléna Jašová
    Cells.2019; 8(11): 1449.     CrossRef
  • NDUFAB1 protects against obesity and insulin resistance by enhancing mitochondrial metabolism
    Rufeng Zhang, Tingting Hou, Heping Cheng, Xianhua Wang
    The FASEB Journal.2019; 33(12): 13310.     CrossRef
  • Mitochondrial Flexibility of Breast Cancers: A Growth Advantage and a Therapeutic Opportunity
    Angelica Avagliano, Maria Rosaria Ruocco, Federica Aliotta, Immacolata Belviso, Antonello Accurso, Stefania Masone, Stefania Montagnani, Alessandro Arcucci
    Cells.2019; 8(5): 401.     CrossRef
  • Effects of intermittent hypoxia training on leukocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and blood insulin level in prediabetes patients
    Tetiana V. Serebrovska, Alla G. Portnychenko, Vladimir I. Portnichenko, Lei Xi, Egor Egorov, Ivanna Antoniuk-Shcheglova, Svitlana Naskalova, Valeriy B. Shatylo
    European Journal of Applied Physiology.2019; 119(3): 813.     CrossRef
Original Article
Others
Rg3 Improves Mitochondrial Function and the Expression of Key Genes Involved in Mitochondrial Biogenesis in C2C12 Myotubes
Min Joo Kim, Young Do Koo, Min Kim, Soo Lim, Young Joo Park, Sung Soo Chung, Hak C. Jang, Kyong Soo Park
Diabetes Metab J. 2016;40(5):406-413.   Published online August 12, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.5.406
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AbstractAbstract PDFPubReader   
Background

Panax ginseng has glucose-lowering effects, some of which are associated with the improvement in insulin resistance in skeletal muscle. Because mitochondria play a pivotal role in the insulin resistance of skeletal muscle, we investigated the effects of the ginsenoside Rg3, one of the active components of P. ginseng, on mitochondrial function and biogenesis in C2C12 myotubes.

Methods

C2C12 myotubes were treated with Rg3 for 24 hours. Insulin signaling pathway proteins were examined by Western blot. Cellular adenosine triphosphate (ATP) levels and the oxygen consumption rate were measured. The protein or mRNA levels of mitochondrial complexes were evaluated by Western blot and quantitative reverse transcription polymerase chain reaction analysis.

Results

Rg3 treatment to C2C12 cells activated the insulin signaling pathway proteins, insulin receptor substrate-1 and Akt. Rg3 increased ATP production and the oxygen consumption rate, suggesting improved mitochondrial function. Rg3 increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α, nuclear respiratory factor 1, and mitochondrial transcription factor, which are transcription factors related to mitochondrial biogenesis. Subsequent increased expression of mitochondrial complex IV and V was also observed.

Conclusion

Our results suggest that Rg3 improves mitochondrial function and the expression of key genes involved in mitochondrial biogenesis, leading to an improvement in insulin resistance in skeletal muscle. Rg3 may have the potential to be developed as an anti-hyperglycemic agent.

Citations

Citations to this article as recorded by  
  • Comparison of Ginseng Leaf Extract and Its Acid-Treated Form, UG0712 Between Their Effects on Exercise Performance in Mice
    Young Jin Lee, Su Hyun Yu, Gwang Yeong Seok, Su Yeon Kim, Mi Jeong Kim, Inhye Jeong, Wan Heo, Bo Su Lee, Seon Gil Do, Bok Kyung Han, Young Jun Kim
    Food Supplements and Biomaterials for Health.2024;[Epub]     CrossRef
  • Ginsenosides for the treatment of insulin resistance and diabetes: Therapeutic perspectives and mechanistic insights
    Tae Hyun Kim
    Journal of Ginseng Research.2024;[Epub]     CrossRef
  • Preparation and bioactivity of the rare ginsenosides Rg3 and Rh2: An updated review
    Wenqi Xu, Wei Lyu, Cuicui Duan, Fumin Ma, Xiaolei Li, Dan Li
    Fitoterapia.2023; 167: 105514.     CrossRef
  • Ginsenoside Rc, an Active Component of Panax ginseng, Alleviates Oxidative Stress-Induced Muscle Atrophy via Improvement of Mitochondrial Biogenesis
    Aeyung Kim, Sang-Min Park, No Soo Kim, Haeseung Lee
    Antioxidants.2023; 12(8): 1576.     CrossRef
  • Ginsenoside Rg3 protects glucocorticoid‑induced muscle atrophy in vitro through improving mitochondrial biogenesis and myotube growth
    Ryuni Kim, Jee Kim, Sang-Jin Lee, Gyu-Un Bae
    Molecular Medicine Reports.2022;[Epub]     CrossRef
  • Beneficial Effects of Walnut Oligopeptides on Muscle Loss in Senescence-Accelerated Mouse Prone-8 (SAMP8) Mice: Focusing on Mitochondrial Function
    Rui Fan, Yuntao Hao, Qian Du, Jiawei Kang, Meihong Xu, Yong Li
    Nutrients.2022; 14(10): 2051.     CrossRef
  • Ginseng and ginsenosides: Therapeutic potential for sarcopenia
    Weiwei Zha, Yuanhai Sun, Wenwen Gong, Linghuan Li, Wonnam Kim, Hanbing Li
    Biomedicine & Pharmacotherapy.2022; 156: 113876.     CrossRef
  • Bioactive Oligopeptides from Ginseng (Panax ginseng Meyer) Suppress Oxidative Stress-Induced Senescence in Fibroblasts via NAD+/SIRT1/PGC-1α Signaling Pathway
    Na Zhu, Mei-Hong Xu, Yong Li
    Nutrients.2022; 14(24): 5289.     CrossRef
  • Review of ginsenosides targeting mitochondrial function to treat multiple disorders: Current status and perspectives
    Qingxia Huang, Song Gao, Daqing Zhao, Xiangyan Li
    Journal of Ginseng Research.2021; 45(3): 371.     CrossRef
  • The Effects of Korean Red Ginseng on Biological Aging and Antioxidant Capacity in Postmenopausal Women: A Double-Blind Randomized Controlled Study
    Tae-Ha Chung, Ji-Hye Kim, So-Young Seol, Yon-Ji Kim, Yong-Jae Lee
    Nutrients.2021; 13(9): 3090.     CrossRef
  • A comprehensive review on the phytochemistry, pharmacokinetics, and antidiabetic effect of Ginseng
    Yage Liu, Hao Zhang, Xuan Dai, Ruyuan Zhu, Beibei Chen, Bingke Xia, Zimengwei Ye, Dandan Zhao, Sihua Gao, Alexander N. Orekhov, Dongwei Zhang, Lili Wang, Shuzhen Guo
    Phytomedicine.2021; 92: 153717.     CrossRef
  • Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes
    Federica Zatterale, Michele Longo, Jamal Naderi, Gregory Alexander Raciti, Antonella Desiderio, Claudia Miele, Francesco Beguinot
    Frontiers in Physiology.2020;[Epub]     CrossRef
  • Stereoisomer-specific ginsenoside 20(S)-Rg3 reverses replicative senescence of human diploid fibroblasts via Akt-mTOR-Sirtuin signaling
    Kyeong-Eun Yang, Hyun-Jin Jang, In-Hu Hwang, Eun Mi Hong, Min-Goo Lee, Soon Lee, Ik-Soon Jang, Jong-Soon Choi
    Journal of Ginseng Research.2020; 44(2): 341.     CrossRef
  • Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: Pharmacology and mechanisms
    Wenxiang Fan, Yongliang Huang, Hui Zheng, Shuiqin Li, Zhuohong Li, Li Yuan, Xi Cheng, Chengshi He, Jianfeng Sun
    Biomedicine & Pharmacotherapy.2020; 132: 110915.     CrossRef
  • Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells
    Taeui Hong, Moon Young Kim, Dat Da Ly, Su Jung Park, Young Woo Eom, Kyu-Sang Park, Soon Koo Baik
    Stem Cell Research & Therapy.2020;[Epub]     CrossRef
  • Mitochondrial Dysfunction in Adipocytes as a Primary Cause of Adipose Tissue Inflammation
    Chang-Yun Woo, Jung Eun Jang, Seung Eun Lee, Eun Hee Koh, Ki-Up Lee
    Diabetes & Metabolism Journal.2019; 43(3): 247.     CrossRef
  • Ginsenoside Rg3 upregulates myotube formation and mitochondrial function, thereby protecting myotube atrophy induced by tumor necrosis factor-alpha
    Sang-Jin Lee, Ju Hyun Bae, Hani Lee, Hyunji Lee, Jongsun Park, Jong-Sun Kang, Gyu-Un Bae
    Journal of Ethnopharmacology.2019; 242: 112054.     CrossRef
  • Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes
    Litao Bai, Jialiang Gao, Fan Wei, Jing Zhao, Danwei Wang, Junping Wei
    Frontiers in Pharmacology.2018;[Epub]     CrossRef
  • Ginseng and obesity
    Zhipeng Li, Geun Eog Ji
    Journal of Ginseng Research.2018; 42(1): 1.     CrossRef
  • Molecular signaling of ginsenosides Rb1, Rg1, and Rg3 and their mode of actions
    Padmanaban Mohanan, Sathiyamoorthy Subramaniyam, Ramya Mathiyalagan, Deok-Chun Yang
    Journal of Ginseng Research.2018; 42(2): 123.     CrossRef
  • Inactivation of glycogen synthase kinase-3β (GSK-3β) enhances skeletal muscle oxidative metabolism
    W.F. Theeuwes, H.R. Gosker, R.C.J. Langen, K.J.P. Verhees, N.A.M. Pansters, A.M.W.J. Schols, A.H.V. Remels
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2017; 1863(12): 3075.     CrossRef
  • Anti-Fatigue Effects of Small Molecule Oligopeptides Isolated from Panax ginseng C. A. Meyer in Mice
    Lei Bao, Xiaxia Cai, Junbo Wang, Yuan Zhang, Bin Sun, Yong Li
    Nutrients.2016; 8(12): 807.     CrossRef

Diabetes Metab J : Diabetes & Metabolism Journal