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Metabolic Risk/Epidemiology
Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism
Tong Bu, Ziyan Sun, Yi Pan, Xia Deng, Guoyue Yuan
Received August 14, 2023  Accepted January 1, 2024  Published online April 1, 2024  
DOI: https://doi.org/10.4093/dmj.2023.0277    [Epub ahead of print]
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  • 15 Download
AbstractAbstract PDFPubReader   ePub   
Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone that is mainly expressed in the intestine and hypothalamus. In recent years, basic and clinical studies have shown that GLP-1 is closely related to lipid metabolism, and it can participate in lipid metabolism by inhibiting fat synthesis, promoting fat differentiation, enhancing cholesterol metabolism, and promoting adipose browning. GLP-1 plays a key role in the occurrence and development of metabolic diseases such as obesity, nonalcoholic fatty liver disease, and atherosclerosis by regulating lipid metabolism. It is expected to become a new target for the treatment of metabolic disorders. The effects of GLP-1 and dual agonists on lipid metabolism also provide a more complete treatment plan for metabolic diseases. This article reviews the recent research progress of GLP-1 in lipid metabolism.
Original Article
Lifestyle
Associations of Ultra-Processed Food Intake with Body Fat and Skeletal Muscle Mass by Sociodemographic Factors
Sukyoung Jung, Jaehee Seo, Jee Young Kim, Sohyun Park
Received September 19, 2023  Accepted November 7, 2023  Published online February 2, 2024  
DOI: https://doi.org/10.4093/dmj.2023.0335    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The effects of excessive ultra-processed food (UPF) consumption on body composition measures or sociodemographic disparities are understudied in Korea. We aimed to investigate the association of UPF intake with percent body fat (PBF) and percent appendicular skeletal muscle mass (PASM) by sociodemographic status in adults.
Methods
This study used data from the Korea National Health and Nutrition Examination Survey 2008–2011 (n=11,123 aged ≥40 years). We used a NOVA system to classify all foods reported in a 24-hour dietary recall, and the percentage of energy intake (%kcal) from UPFs was estimated. PBF and PASM were measured by dual-energy X-ray absorptiometry. Tertile (T) 3 of PBF indicated adiposity and T1 of PASM indicated low skeletal muscle mass, respectively. Multinomial logistic regression models were used to estimate odds ratios (OR) with 95% confidence interval (CI) after adjusting covariates.
Results
UPF intake was positively associated with PBF-defined adiposity (ORper 10% increase, 1.04; 95% CI, 1.002 to 1.08) and low PASM (ORper 10% increase, 1.05; 95% CI, 1.01 to 1.09). These associations were stronger in rural residents (PBF: ORper 10% increase, 1.14; 95% CI, 1.06 to 1.23; PASM: ORper 10% increase, 1.15; 95% CI, 1.07 to 1.23) and not college graduates (PBF: ORper 10% increase, 1.06; 95% CI, 1.02 to 1.11; PASM: ORper 10% increase, 1.07; 95% CI, 1.03 to 1.12) than their counterparts.
Conclusion
A higher UPF intake was associated with higher adiposity and lower skeletal muscle mass among Korean adults aged 40 years and older, particularly in those from rural areas and with lower education levels.
Reviews
Pathophysiology
Epicardial Adipose Tissue and Heart Failure, Friend or Foe?
Dong-Hyuk Cho, Seong-Mi Park
Received June 20, 2023  Accepted December 11, 2023  Published online February 2, 2024  
DOI: https://doi.org/10.4093/dmj.2023.0190    [Epub ahead of print]
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  • 1 Crossref
AbstractAbstract PDFPubReader   ePub   
Heart failure (HF) management guidelines recommend individualized assessments based on HF phenotypes. Adiposity is a known risk factor for HF. Recently, there has been an increased interest in organ-specific adiposity, specifically the role of the epicardial adipose tissue (EAT), in HF risk. EAT is easily assessable through various imaging modalities and is anatomically and functionally connected to the myocardium. In pathological conditions, EAT secretes inflammatory cytokines, releases excessive fatty acids, and increases mechanical load on the myocardium, resulting in myocardial remodeling. EAT plays a pathophysiological role in characterizing both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). In HFrEF, EAT volume is reduced, reflecting an impaired metabolic reservoir, whereas in HFpEF, the amount of EAT is associated with worse biomarker and hemodynamic profiles, indicating increased EAT activity. Studies have examined the possibility of therapeutically targeting EAT, and recent studies using sodium glucose cotransporter 2 inhibitors have shown potential in reducing EAT volume. However, further research is required to determine the clinical implications of reducing EAT activity in patients with HF.

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  • New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review
    Jorge E. Jalil, Luigi Gabrielli, María Paz Ocaranza, Paul MacNab, Rodrigo Fernández, Bruno Grassi, Paulina Jofré, Hugo Verdejo, Monica Acevedo, Samuel Cordova, Luis Sanhueza, Douglas Greig
    International Journal of Molecular Sciences.2024; 25(8): 4407.     CrossRef
Basic Research
Adipose Tissue and Metabolic Health
Sung-Min An, Seung-Hee Cho, John C. Yoon
Diabetes Metab J. 2023;47(5):595-611.   Published online July 24, 2023
DOI: https://doi.org/10.4093/dmj.2023.0011
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AbstractAbstract PDFPubReader   ePub   
In this review, we provide a brief synopsis of the connections between adipose tissue and metabolic health and highlight some recent developments in understanding and exploiting adipocyte biology. Adipose tissue plays critical roles in the regulation of systemic glucose and lipid metabolism and secretes bioactive molecules possessing endocrine, paracrine, and autocrine functions. Dysfunctional adipose tissue has a detrimental impact on metabolic health and is intimately involved in key aspects of metabolic diseases such as insulin resistance, lipid overload, inflammation, and organelle stress. Differences in the distribution of fat depots and adipose characteristics relate to divergent degrees of metabolic dysfunction found in metabolically healthy and unhealthy obese individuals. Thermogenic adipocytes increase energy expenditure via mitochondrial uncoupling or adenosine triphosphate-consuming futile substrate cycles, while functioning as a metabolic sink and participating in crosstalk with other metabolic organs. Manipulation of adipose tissue provides a wealth of opportunities to intervene and combat the progression of associated metabolic diseases. We discuss current treatment modalities for obesity including incretin hormone analogs and touch upon emerging strategies with therapeutic potential including exosome-based therapy, pharmacological activation of brown and beige adipocyte thermogenesis, and administration or inhibition of adipocyte-derived factors.

Citations

Citations to this article as recorded by  
  • Pharmacological targets at the lysosomal autophagy–NLRP3 inflammasome crossroads
    Srinivasa Reddy Bonam, Dylan Mastrippolito, Philippe Georgel, Sylviane Muller
    Trends in Pharmacological Sciences.2024; 45(1): 81.     CrossRef
  • Senescent adipocytes and type 2 diabetes – current knowledge and perspective concepts
    Weronika Kruczkowska, Julia Gałęziewska, Mateusz Kciuk, Adrianna Gielecińska, Elżbieta Płuciennik, Zbigniew Pasieka, Lin-Yong Zhao, Yi-Jin Yu, Damian Kołat, Żaneta Kałuzińska-Kołat
    Biomolecular Concepts.2024;[Epub]     CrossRef
  • Visceral Adipose Tissue: The Hidden Culprit for Type 2 Diabetes
    Sneha Dhokte, Krzysztof Czaja
    Nutrients.2024; 16(7): 1015.     CrossRef
  • Beyond the Cold: Activating Brown Adipose Tissue as an Approach to Combat Obesity
    Cristina Elena Negroiu, Iulia Tudorașcu, Cristina Maria Bezna, Sanziana Godeanu, Marina Diaconu, Raluca Danoiu, Suzana Danoiu
    Journal of Clinical Medicine.2024; 13(7): 1973.     CrossRef
Original Article
Metabolic Risk/Epidemiology
Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography
Hwi Seung Kim, Jiwoo Lee, Eun Hee Kim, Min Jung Lee, In Young Bae, Woo Je Lee, Joong-Yeol Park, Hong-Kyu Kim, Chang Hee Jung
Diabetes Metab J. 2023;47(1):104-117.   Published online January 26, 2023
DOI: https://doi.org/10.4093/dmj.2022.0081
  • 3,238 View
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  • 7 Web of Science
  • 6 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The association of myosteatosis measured using visual muscular quality map in computed tomography (CT) with nonalcoholic fatty liver disease (NAFLD), its severity, and fibrosis was analyzed in a large population.
Methods
Subjects (n=13,452) with abdominal CT between 2012 and 2013 were measured total abdominal muscle area (TAMA) at L3 level. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, NAMA/TAMA, and LAMA/BMI. NAFLD and its severity were assessed by ultrasonography, and liver fibrosis was measured by calculating the NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB-4) scores.
Results
According to multiple logistic regression analyses, as quartiles of SMA/BMI, NAMA/BMI, and NAMA/TAMA increased, the odds ratios (ORs) for NAFLD decreased in each sex (P for trend <0.001 for all). The ORs of moderate/severe NAFLD were significantly higher in the Q1 group than in the Q4 group for SMA/BMI, NAMA/BMI, and NAMA/TAMA in men. The ORs of intermediate/high liver fibrosis scores assessed by NFS and FIB-4 scores increased linearly with decreasing quartiles for SMA/BMI, NAMA/BMI, and NAMA/TAMA in each sex (P for trend <0.001 for all). Conversely, the risk for NAFLD and fibrosis were positively associated with LAMA/BMI quartiles in each sex (P for trend <0.001 for all).
Conclusion
A higher proportion of good quality muscle was associated with lower risks of NAFLD and fibrosis.

Citations

Citations to this article as recorded by  
  • Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography (Diabetes Metab J 2023;47:104-17)
    Hwi Seung Kim, Hong-Kyu Kim, Chang Hee Jung
    Diabetes & Metabolism Journal.2023; 47(2): 304.     CrossRef
  • Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography (Diabetes Metab J 2023;47:104-17)
    Eun Roh
    Diabetes & Metabolism Journal.2023; 47(2): 301.     CrossRef
  • Sarcopenia, a condition shared by various diseases: can we alleviate or delay the progression?
    Giovanni Tarantino, Gaia Sinatti, Vincenzo Citro, Silvano Santini, Clara Balsano
    Internal and Emergency Medicine.2023; 18(7): 1887.     CrossRef
  • Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity
    Hong-Kyu Kim, Sung-Jin Bae, Min Jung Lee, Eun Hee Kim, Hana Park, Hwi Seung Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee, Jaewon Choe
    Clinical and Molecular Hepatology.2023; 29(4): 987.     CrossRef
  • Current view of the surgical anatomy of the anterolateral abdominal wall muscles and their aponeuroses
    A.V. Pavlov, A.S. Baranova, A.V. Fedoseyev, A.I. Vvedensky, G.S. Lazutina, N.V. Ovchinnikova, I.V. Bakharev
    Operativnaya khirurgiya i klinicheskaya anatomiya (Pirogovskii nauchnyi zhurnal).2023; 7(3): 44.     CrossRef
  • Muscle Fat Content Is Associated with Nonalcoholic Fatty Liver Disease and Liver Fibrosis in Chinese Adults
    W. Guo, X. Zhao, D. Cheng, X. Liang, M. Miao, X. Li, J. Lu, N. Xu, Shuang Hu, Qun Zhang
    The Journal of nutrition, health and aging.2023; 27(11): 960.     CrossRef
Reviews
Basic Research
Multiple Roles of Sirtuin 6 in Adipose Tissue Inflammation
Eun Ju Bae, Byung-Hyun Park
Diabetes Metab J. 2023;47(2):164-172.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2022.0270
  • 3,743 View
  • 229 Download
  • 4 Web of Science
  • 2 Crossref
AbstractAbstract PDFPubReader   ePub   
Adipose tissue (AT) inflammation is strongly associated with obesity-induced insulin resistance. When subjected to metabolic stress, adipocytes become inflamed and secrete a plethora of cytokines and chemokines, which recruit circulating immune cells to AT. Although sirtuin 6 (Sirt6) is known to control genomic stabilization, aging, and cellular metabolism, it is now understood to also play a pivotal role in the regulation of AT inflammation. Sirt6 protein levels are reduced in the AT of obese humans and animals and increased by weight loss. In this review, we summarize the potential mechanism of AT inflammation caused by impaired action of Sirt6 from the immune cells’ point of view. We first describe the properties and functions of immune cells in obese AT, with an emphasis on discrete macrophage subpopulations which are central to AT inflammation. We then highlight data that links Sirt6 to functional phenotypes of AT inflammation. Importantly, we discuss in detail the effects of Sirt6 deficiency in adipocytes, macrophages, and eosinophils on insulin resistance or AT browning. In our closing perspectives, we discuss emerging issues in this field that require further investigation.

Citations

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  • The Role of Increased Expression of Sirtuin 6 in the Prevention of Premature Aging Pathomechanisms
    Adrianna Dzidek, Olga Czerwińska-Ledwig, Małgorzata Żychowska, Wanda Pilch, Anna Piotrowska
    International Journal of Molecular Sciences.2023; 24(11): 9655.     CrossRef
  • Exploring the Influence of Age, Gender and Body Mass Index on Colorectal Cancer Location
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Metabolic risk/Epidemiology
Obesity, Diabetes, and Increased Cancer Progression
Dae-Seok Kim, Philipp E. Scherer
Diabetes Metab J. 2021;45(6):799-812.   Published online November 22, 2021
DOI: https://doi.org/10.4093/dmj.2021.0077
  • 14,145 View
  • 666 Download
  • 70 Web of Science
  • 76 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Rates of obesity and diabetes have increased significantly over the past decades and the prevalence is expected to continue to rise further in the coming years. Many observations suggest that obesity and diabetes are associated with an increased risk of developing several types of cancers, including liver, pancreatic, endometrial, colorectal, and post-menopausal breast cancer. The path towards developing obesity and diabetes is affected by multiple factors, including adipokines, inflammatory cytokines, growth hormones, insulin resistance, and hyperlipidemia. The metabolic abnormalities associated with changes in the levels of these factors in obesity and diabetes have the potential to significantly contribute to the development and progression of cancer through the regulation of distinct signaling pathways. Here, we highlight the cellular and molecular pathways that constitute the links between obesity, diabetes, cancer risk and mortality. This includes a description of the existing evidence supporting the obesity-driven morphological and functional alternations of cancer cells and adipocytes through complex interactions within the tumor microenvironment.

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    Kexin Zhang, Chengxia Kan, Fang Han, Jingwen Zhang, Chuanhua Ding, Zhentao Guo, Na Huang, Yang Zhang, Ningning Hou, Xiaodong Sun
    JAMA Pediatrics.2023; 177(8): 837.     CrossRef
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    Hyun Jung Park, Sung Ja Rhie, Insop Shim
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    Elad Sharon, Megan Othus, Zoe Eloise Quandt
    Cancer.2023; 129(18): 2769.     CrossRef
  • Ultra-Processed Food Consumption and Obesity in Korean Adults
    Jee-Seon Shim, Kyoung Hwa Ha, Dae Jung Kim, Hyeon Chang Kim
    Diabetes & Metabolism Journal.2023; 47(4): 547.     CrossRef
  • Decoding the role of leptin and adiponectin in obesity-related gastrointestinal cancer
    Vanda Marques, Fabiola Arella, Marta B. Afonso, André A. Santos, Cecília M.P. Rodrigues
    Clinical Science.2023; 137(15): 1095.     CrossRef
  • Diabetes and two kinds of primary tumors in a patient with thalassemia: a case report and literature review
    Xiaoyan Yu, Yi Peng, Tingting Nie, Wenjia Sun, Yajuan Zhou
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Metabolic Risk/Epidemiology
Computed Tomography-Derived Myosteatosis and Metabolic Disorders
Iva Miljkovic, Chantal A. Vella, Matthew Allison
Diabetes Metab J. 2021;45(4):482-491.   Published online July 30, 2021
DOI: https://doi.org/10.4093/dmj.2020.0277
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The role of ectopic adipose tissue infiltration into skeletal muscle (i.e., myosteatosis) for metabolic disorders has received considerable and increasing attention in the last 10 years. The purpose of this review was to evaluate and summarize existing studies focusing on computed tomography (CT)-derived measures of myosteatosis and metabolic disorders. There is consistent evidence that CT-derived myosteatosis contributes to dysglycemia, insulin resistance, type 2 diabetes mellitus, and inflammation, and, to some extent, dyslipidemia, independent of general obesity, visceral fat, and other relevant risk factors, suggesting that it may serve as a tool for metabolic risk prediction. Identification of which muscles should be examined, and the standardized CT protocols to be employed, are necessary to enhance the applicability of findings from epidemiologic studies of myosteatosis. Additional and longer longitudinal studies are necessary to confirm a role of myosteatosis in the development of type 2 diabetes mellitus, and examine these associations in a variety of muscles across multiple race/ethnic populations. Given the emerging role of myosteatosis in metabolic health, well-designed intervention studies are needed to investigate relevant lifestyle and pharmaceutical approaches.

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Basic Research
Brown Fat as a Regulator of Systemic Metabolism beyond Thermogenesis
Okamatsu-Ogura Yuko, Masayuki Saito
Diabetes Metab J. 2021;45(6):840-852.   Published online June 25, 2021
DOI: https://doi.org/10.4093/dmj.2020.0291
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Brown adipose tissue (BAT) is a specialized tissue for nonshivering thermogenesis to dissipate energy as heat. Although BAT research has long been limited mostly in small rodents, the rediscovery of metabolically active BAT in adult humans has dramatically promoted the translational studies on BAT in health and diseases. Moreover, several remarkable advancements have been made in brown fat biology over the past decade: The molecular and functional analyses of inducible thermogenic adipocytes (socalled beige adipocytes) arising from a developmentally different lineage from classical brown adipocytes have been accelerated. In addition to a well-established thermogenic activity of uncoupling protein 1 (UCP1), several alternative thermogenic mechanisms have been discovered, particularly in beige adipocytes. It has become clear that BAT influences other peripheral tissues and controls their functions and systemic homeostasis of energy and metabolic substrates, suggesting BAT as a metabolic regulator, other than for thermogenesis. This notion is supported by discovering that various paracrine and endocrine factors are secreted from BAT. We review the current understanding of BAT pathophysiology, particularly focusing on its role as a metabolic regulator in small rodents and also in humans.

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Original Articles
Basic Research
Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway
Ji-Yeon Lee, Minyoung Lee, Ji Young Lee, Jaehyun Bae, Eugene Shin, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
Diabetes Metab J. 2021;45(6):921-932.   Published online February 22, 2021
DOI: https://doi.org/10.4093/dmj.2020.0187
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism.
Methods
Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks.
Results
The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue.
Conclusion
SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.

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Others
Can Habitual Exercise Help Reduce Serum Concentrations of Lipophilic Chemical Mixtures? Association between Physical Activity and Persistent Organic Pollutants
Yu-Mi Lee, Ji-Yeon Shin, Se-A Kim, David R. Jacobs, Duk-Hee Lee
Diabetes Metab J. 2020;44(5):764-774.   Published online May 11, 2020
DOI: https://doi.org/10.4093/dmj.2019.0158
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Low-dose persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs), have emerged as a new risk factor of many chronic diseases. As serum concentrations of POPs in humans are mainly determined by both their release from adipose tissue to circulation and their elimination from circulation, management of these internal pathways may be important in controlling the serum concentrations of POPs. As habitual physical activity can increase the elimination of POPs from circulation, we evaluated whether chronic physical activity is related to low serum POP concentrations.

Methods

A cross-sectional study of 1,850 healthy adults (age ≥20 years) without cardio-metabolic diseases who participated in the U.S. National Health and Nutrition Examination Survey 1999 to 2004 was conducted. Information on moderate or vigorous leisure-time physical activity was obtained based on questionnaires. Serum concentrations of OCPs and polychlorinated biphenyls were investigated as typical POPs.

Results

Serum concentrations of OCPs among physically active subjects were significantly lower than those among physically inactive subjects (312.8 ng/g lipid vs. 538.0 ng/g lipid, P<0.001). This difference was maintained after adjustment for potential confounders. When analyses were restricted to physically active subjects, there were small decreases in the serum concentrations of OCPs with increasing duration of physical activity, showing a curvilinear relationship over the whole range of physical activity (Pquadratic <0.001). In analyses stratified by age, sex, body mass index, and smoking status, a strong inverse association was similarly observed among all subgroups.

Conclusion

Physical activity may assist in decreasing serum concentrations of lipophilic chemical mixtures such as OCPs.

Citations

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Reviews
Obesity and Metabolic Syndrome
Two Faces of White Adipose Tissue with Heterogeneous Adipogenic Progenitors
Injae Hwang, Jae Bum Kim
Diabetes Metab J. 2019;43(6):752-762.   Published online December 26, 2019
DOI: https://doi.org/10.4093/dmj.2019.0174
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AbstractAbstract PDFPubReader   

Chronic energy surplus increases body fat, leading to obesity. Since obesity is closely associated with most metabolic complications, pathophysiological roles of adipose tissue in obesity have been intensively studied. White adipose tissue is largely divided into subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). These two white adipose tissues are similar in their appearance and lipid storage functions. Nonetheless, emerging evidence has suggested that SAT and VAT have different characteristics and functional roles in metabolic regulation. It is likely that there are intrinsic differences between VAT and SAT. In diet-induced obese animal models, it has been reported that adipogenic progenitors in VAT rapidly proliferate and differentiate into adipocytes. In obesity, VAT exhibits elevated inflammatory responses, which are less prevalent in SAT. On the other hand, SAT has metabolically beneficial effects. In this review, we introduce recent studies that focus on cellular and molecular components modulating adipogenesis and immune responses in SAT and VAT. Given that these two fat depots show different functions and characteristics depending on the nutritional status, it is feasible to postulate that SAT and VAT have different developmental origins with distinct adipogenic progenitors, which would be a key determining factor for the response and accommodation to metabolic input for energy homeostasis.

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Pathophysiology
Regulation of Systemic Glucose Homeostasis by T Helper Type 2 Cytokines
Yea Eun Kang, Hyun Jin Kim, Minho Shong
Diabetes Metab J. 2019;43(5):549-559.   Published online October 24, 2019
DOI: https://doi.org/10.4093/dmj.2019.0157
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AbstractAbstract PDFPubReader   

Obesity results in an inflammatory microenvironment in adipose tissue, leading to the deterioration of tissue protective mechanisms. Although recent studies suggested the importance of type 2 immunity in an anti-inflammatory microenvironment in adipose tissue, the regulatory effects of T helper 2 (Th2) cytokines on systemic metabolic regulation are not fully understood. Recently, we identified the roles of the Th2 cytokine (interleukin 4 [IL-4] and IL-13)-induced adipokine, growth differentiation factor 15 (GDF15), in adipose tissue in regulating systemic glucose metabolism via signal transducer and activator of transcription 6 (STAT6) activation. Moreover, we showed that mitochondrial oxidative phosphorylation is required to maintain these macrophage-regulating autocrine and paracrine signaling pathways via Th2 cytokine-induced secretion of GDF15. In this review, we discuss how the type 2 immune response and Th2 cytokines regulate metabolism in adipose tissue. Specifically, we review the systemic regulatory roles of Th2 cytokines in metabolic disease and the role of mitochondria in maintenance of type 2 responses in adipose tissue homeostasis.

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Original Article
Epidemiology
Longitudinal Changes of Body Composition Phenotypes and Their Association with Incident Type 2 Diabetes Mellitus during a 5-Year Follow-up in Koreans
Hong-Kyu Kim, Min Jung Lee, Eun-Hee Kim, Sung-Jin Bae, Jaewon Choe, Chul-Hee Kim, Joong-Yeol Park
Diabetes Metab J. 2019;43(5):627-639.   Published online April 19, 2019
DOI: https://doi.org/10.4093/dmj.2018.0141
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

To elucidate longitudinal changes of complex body composition phenotypes and their association with incident type 2 diabetes mellitus.

Methods

A total of 17,280 (mean age, 48.1±8.2 years) Korean adults who underwent medical check-ups were included. The mean follow-up duration was 5.5±0.5 years. Body compositions were assessed using a bioelectrical impedance analysis. Four body composition phenotypes were defined using the median of appendicular skeletal muscle mass (ASM) index and fat mass index: low muscle/low fat (LM/LF); high muscle (HM)/LF; LM/high fat (HF); and HM/HF groups.

Results

Of the individuals in the LM/LF or HM/HF groups, over 60% remained in the same group, and over 30% were moved to the LM/HF group. Most of the LM/HF group remained in this group. In the baseline HM/LF group, approximately 30% stayed in the group, and the remaining individuals transitioned to the three other groups in similar proportions. Incident diabetes was significantly lower in participants who remained in the HM/LF group than those who transitioned to the LM/LF or LM/HF group from the baseline HM/LF group in men. ASM index was significantly associated with a decreased risk for incident diabetes in men regardless of obesity status (adjusted odds ratio [OR], 0.71 per kg/m2; 95% confidence interval [CI], 0.52 to 0.97 in non-obese) (adjusted OR, 0.87; 95% CI, 0.77 to 0.98 in obese) after adjusting for other strong risk factors (e.g., baseline glycosylated hemoglobin and homeostasis model assessment of insulin resistance).

Conclusion

Maintenance of ASM may be protective against the development of type 2 diabetes mellitus in men, regardless of obesity status.

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Brief Report
Complication
Morphologic Comparison of Peripheral Nerves in Adipocyte Tissue from db/db Diabetic versus Normal Mice
Kyung Ae Lee, Na Young Lee, Tae Sun Park, Heung Yong Jin
Diabetes Metab J. 2018;42(2):169-172.   Published online March 21, 2018
DOI: https://doi.org/10.4093/dmj.2018.42.2.169
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AbstractAbstract PDFPubReader   

Present study investigated the morphologic changes of autonomic nerves in the adipose tissue in diabetic animal model. Male obese type 2 diabetic db/db mice and age matched non-diabetic db/m control mice were used. Epididymal adipose tissue from diabetic db/db mice with that from control heterozygous db/m mice was compared using confocal microscopy-based method to visualize intact whole adipose tissue. Immunohistochemistry with tyrosine hydroxylase for sympathetic (SP), choline acetyltransferase for parasympathetic (PSP), and protein gene product 9.5 (PGP 9.5) for whole autonomic nerves was performed. The quantity of immunostained portion of SP, PSP, and PGP 9.5 stained nerve fibers showed decreased trend in diabetic group; however, the ratio of SP/PSP of adipose tissue was higher in diabetic group compared with control group as follows (0.70±0.30 vs. 0.95±0.25, P<0.05; normal vs. diabetic, respectively). Both SP and PSP nerve fibers were observed in white adipose tissue and PSP nerve fibers were suggested as more decreased in diabetes based on our observation.


Diabetes Metab J : Diabetes & Metabolism Journal