- Metabolic Risk/Epidemiology
- Effect of Low-Dose Persistent Organic Pollutants on Mitochondrial Function: Human and in Vitro Evidence
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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
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Diabetes Metab J. 2022;46(4):592-604. Published online January 26, 2022
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DOI: https://doi.org/10.4093/dmj.2021.0132
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Abstract
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- 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.
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Citations
Citations to this article as recorded by
- 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 - Obesity paradox can be a fact: unveiling the hidden role of adipose tissue
Duk-Hee Lee European Heart Journal.2024; 45(24): 2167. CrossRef - Reduced bioenergetics and mitochondrial fragmentation in human primary cytotrophoblasts induced by an EGFR-targeting chemical mixture
Anita A. Waye, Elvis Ticiani, Zinat Sharmin, Vanessa Perez Silos, Thilini Perera, Alex Tu, Irina A. Buhimschi, Carlos A. Murga-Zamalloa, Ying S. Hu, Almudena Veiga-Lopez Chemosphere.2024; 364: 143301. 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
- Others
- Can Habitual Exercise Help Reduce Serum Concentrations of Lipophilic Chemical Mixtures? Association between Physical Activity and Persistent Organic Pollutants
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Yu-Mi Lee, Ji-Yeon Shin, Se-A Kim, David R. Jacobs, Duk-Hee Lee
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Diabetes Metab J. 2020;44(5):764-774. Published online May 11, 2020
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DOI: https://doi.org/10.4093/dmj.2019.0158
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6,100
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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.
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Citations
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Quentin A. Serrano, Sébastien Le Garf, Vincent Martin, Serge S. Colson, Nicolas Chevalier International Journal of Molecular Sciences.2024; 25(2): 883. CrossRef - Untargeted metabolomics reveal signatures of a healthy lifestyle
Wimal Pathmasiri, Blake R. Rushing, Susan McRitchie, Mansi Choudhari, Xiuxia Du, Alexsandr Smirnov, Matteo Pelleigrini, Michael J. Thompson, Camila A. Sakaguchi, David C. Nieman, Susan J. Sumner Scientific Reports.2024;[Epub] CrossRef - Unraveling the pesticide-diabetes connection: A case-cohort study integrating Mendelian randomization analysis with a focus on physical activity's mitigating effect
Dandan Wei, Jiayu Shi, Zhiwei Chen, Haoran Xu, Xuyan Wu, Yao Guo, Xin Zen, Caini Fan, Xiaotian Liu, Jian Hou, Wenqian Huo, Linlin Li, Tao Jing, Chongjian Wang, Zhenxing Mao Ecotoxicology and Environmental Safety.2024; 283: 116778. CrossRef - Prospective study on the joint effect of persistent organic pollutants and glucose metabolism on chronic kidney disease: Modifying effects of lifestyle interventions
Dandan Wei, Jiayu Shi, Haoran Xu, Yao Guo, Xueyan Wu, Zhiwei Chen, Taimeng Chen, Huilin Lou, Erbao Han, Guozhen Han, Yumeng Yan, Xiaotian Liu, Xin Zeng, Caini Fan, Jian Hou, Wenqian Huo, Linlin Li, Tao Jing, Chongjian Wang, Zhenxing Mao Science of The Total Environment.2024; 951: 175694. CrossRef - Associations between polychlorinated biphenyls and cancer risk among type 2 diabetes: The modifying effects of lifestyle
Peiwen Li, Yu Wang, Qianying Liu, Yan Yan, Zhuoya Zhao, Shiyang Zhang, Chengyong Jia, Jun An, Cheng Xu, Xin Zhang, Tao Jing, Huan Guo, Meian He Chemosphere.2024; 366: 143442. CrossRef - Physical exercise and persistent organic pollutants
Chang Liu, Hui sheng Hou Heliyon.2023; 9(9): e19661. CrossRef - Exposure to a low concentration of mixed organochlorine pesticides impairs glucose metabolism and mitochondrial function in L6 myotubes and zebrafish
Chul-Min Park, Ki-Tae Kim, Dong-Young Rhyu Journal of Hazardous Materials.2021; 414: 125437. CrossRef - Can Environmental Pollutants Be a Factor Linking Obesity and COVID-19?
Duk-Hee Lee Journal of Korean Medical Science.2021;[Epub] CrossRef - Letter to the Editor: Effect of fatty fish or nut consumption on concentrations of persistent organic pollutants in overweight or obese men and women: A randomized controlled clinical trial
Yu-Mi Lee, Duk-Hee Lee Nutrition, Metabolism and Cardiovascular Diseases.2020; 30(5): 849. CrossRef - Can habitual exercise really increase serum concentrations of persistent organic pollutants?
Yu-Mi Lee, Duk-Hee Lee Environment International.2020; 140: 105615. CrossRef - Response to correspondence ENVINT_2020_552 “Can habitual exercise really increase serum concentrations of persistent organic pollutants?”
Sidsel L. Domazet, Tina K. Jensen, Anders Grøntved Environment International.2020; 140: 105616. CrossRef
- Others
- Mitochondrial Toxins and Healthy Lifestyle Meet at the Crossroad of Hormesis
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Yu-Mi Lee, Duk-Hee Lee
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Diabetes Metab J. 2019;43(5):568-577. Published online October 24, 2019
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DOI: https://doi.org/10.4093/dmj.2019.0143
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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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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
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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
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- Epidemiology
- Can Air Pollution Biologically Hinder Efforts to Lose Body Weight?
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Duk-Hee Lee
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Diabetes Metab J. 2018;42(4):282-284. Published online August 21, 2018
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DOI: https://doi.org/10.4093/dmj.2018.0139
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- Sex-specific effects of blood cadmium on thyroid hormones and thyroid function status: Korean nationwide cross-sectional study
Seung Min Chung, Jun Sung Moon, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee Journal of Trace Elements in Medicine and Biology.2019; 53: 55. CrossRef
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