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Metabolic syndrome and the environmental pollutants from mitochondrial perspectives

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Abstract

The worldwide epidemic of diabetes and metabolic syndrome in the last few decades cannot be fully accounted for only by changes in the lifestyle factors, such as sedentary lifestyle and overeating. Besides genetic factors, there must be other causes to explain this rapid change. They could not be infectious in nature and induce insulin resistance as key biochemical abnormality. Mitochondrial dysfunction could be underlying mechanism behind the insulin resistance, thus metabolic syndrome. Then there have been increasing number of reports suggesting that chronic exposure to and accumulation of endocrine disrupting chemicals (EDCs), especially so-called the persistent organic pollutants (POPs) within the body might be associated with metabolic syndrome. Combining two concepts, we developed new “EDCs-induced mitochondrial dysfunction hypothesis of metabolic syndrome”. In this review we suggest that classifying those chemicals into 5 groups might be clinically useful considering their removal or avoidance; POPs, non-persistent organic pollutants, heavy metals, air pollutants and drugs. We will also discuss briefly how those insights could be applied to clinical medicine.

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References

  1. Meigs JB. Invited commentary: insulin resistance syndrome? Syndrome X? Multiple metabolic syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors. Am JEpidemiol. 2000;152:908–11.

    Article  CAS  Google Scholar 

  2. Reaven GM. Banting lecture, Role of insulin resistance in human disease. Diabetes. 1998;37:1595–607.

    Article  Google Scholar 

  3. Lee HK, Cho YM, Kwak SH, Lim S, Park KS, Shim EB. Mitochondrial dysfunction and metabolic syndrome-looking for environmental factors. Biochim Biophys Acta. 2010;1800(3):282–9.

    Article  CAS  PubMed  Google Scholar 

  4. Lee HK, Shim EB. Extension of Mitochondria Dysfunction Hypothesis of Metabolic Syndrome to Atherosclerosis with Emphasis on the Endocrine Disrupting Chemicals and Biophysical Laws. J Diabetes Investig. 2013;4(1):19–33.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Meyer JN, Leung MC, Rooney JP, Sendoel A, Hengartner MO, Kisby GE, et al. Mitochondria as a target of environmental toxicants. Toxicol Sci. 2013;134(1):1–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lee DH, Porta M, Jacobs Jr DR, Vandenberg LN. Chlorinated persistent organic pollutants, obesity, and type 2 diabetes. Endocr Rev. 2014;35(4):557–601.

    Article  CAS  PubMed  Google Scholar 

  7. Lee HK, Song JH, Shin CS, Park DJ, Park KS, Lee KU, et al. Decreased mitochondrial DNA content in peripheral blood precedes the development of non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract. 1998;42:161–7.

    Article  CAS  PubMed  Google Scholar 

  8. Jucker BM, Dufour S, Ren J, Cao X, Previs SF, Underhill B, et al. Shulman GI.Assessment of mitochondrial energy coupling in vivo by 13C/31P NMR. Proc Natl Acad Sci U S A. 2000;97:6880–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. 2003;300:1140–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Smith RE. Quantitative relations between liver mitochondria metabolism and total body weight in mammals. Ann NY Acad Sci. 1956;62:403–22.

    Article  CAS  Google Scholar 

  11. Rasmussen UF, Rasmussen HN, Krustrup P, Quistorff B, Saltin B, Bangsbo J. Aerobic metabolism of human quadriceps muscle: in vivo data parallel measurements on isolated mitochondria. Am J Physiol Endocrinol Metab. 2001;280:301–7.

    Google Scholar 

  12. Lee HK. Method of proof and evidences for the concept that mitochondrial genome is a thrifty genome. Diabetes Res Clin Pract. (Suppl. 2) 2001;54–63.

  13. Kleiber M. Body size and metabolism. Hilgardia. 1932;6:315–53.

    Article  CAS  Google Scholar 

  14. West GB, Woodruff WH, Brown JH. Allometric scaling of metabolic rate from molecules and mitochondria to cells and mammals. Proc Natl Acad Sci U S A. 2002;99 Suppl 1:2473–8.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ravussin E, Lillioja S, Knowler WC, Christin L, Freymond D, Abbott WG, et al. Reduced rate of energy expenditure as a risk factor for bodyweight gain. N Engl J Med. 1988;318:467–72.

    Article  CAS  PubMed  Google Scholar 

  16. Chun PW. Why does the human body maintain a constant 37-degree temperature?: thermodynamic switch controls chemical equilibrium in biological systems. Phys Scr. 2005;118:219–22.

    Article  Google Scholar 

  17. Patti ME, Corvera S. The role of mitochondria in the pathogenesis of type 2 diabetes. Endocr Rev. 2010;31(3):364–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Szendroedi J, Phielix E, Roden M. The role of mitochondria in insulin resistance and type 2 diabetes mellitus. Nat Rev Endocrinol. 2012;8(2):92–103.

    Article  CAS  Google Scholar 

  19. Pravenec M, Hyakukoku M, Houstek J, Zidek V, Landa V, Mlejnek P, et al. Direct linkage of mitochondrial genome variation to risk factors for type 2 diabetes in conplastic strains. Genome Res. 2007;17:1319–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fuku N, Park KS, Yamada Y, Nishigaki Y, Cho YM, Matsuo H, et al. Mitochondrial haplogroup N9a confers resistance against type 2 diabetes in Asians. Am J Hum Genet. 2007;80:407–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Park KS, Chan JC, Chuang LM, Suzuki S, Araki E, Nanjo K, et al. A mitochondrial DNA variant at position 16189 is associated with type 2 diabetes mellitus in Asians. Diabetologia. 2008;51:602–8.

    Article  CAS  PubMed  Google Scholar 

  22. Flaquer A, Baumbach C, Kriebel J, Meitinger T, Peters A, Waldenberger M, et al. Mitochondrial Genetic Variants Identified to Be Associated with BMI in Adults. PLoS One. 2014;9(8):e105116.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992;35:595–601.

    Article  CAS  PubMed  Google Scholar 

  24. Knowler WC, Pettitt DJ, Bennett PH, Williams RC. Diabetes mellitus in the Pima Indians: genetic and evolutionary considerations. Am J Phys Anthropol. 1983;62:107–14.

    Article  CAS  PubMed  Google Scholar 

  25. Cannon B, Nedergaard J. Thermogenesis challenges the adipostat hypothesis for body-weight control. Proc Nutr Soc. 2009;68(4):401–7.

    Article  PubMed  Google Scholar 

  26. Koleva DI, Orbetzova MM, Atanassova PK. Adipose tissue hormones and appetite and body weight regulators in insulin resistance. Folia Med (Plovdiv). 2013;55(1):25–32.

    CAS  Google Scholar 

  27. Krebs HA, Eggleston LV. The effect of insulin on oxidations in isolated muscle tissue. Biochem J. 1938;32(5):913913.

    Google Scholar 

  28. Echave P1, Machado-da-Silva G, Arkell RS, Duchen MR, Jacobson J, Mitter R, et al. Extracellular growth factors and mitogens cooperate to drive mitochondrial biogenesis. J Cell Sci. 2009;122(24):4516–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Damstra T, Barlow S, Aake B, Kavlock R, Van Der Kraak G. International Programme on Chemical Safety: Global Assessment of the State-of-the-Science on Endocrine Disruptors. 2002. http://www.who.int/pcs/emerg_site/edc/global_edc_TOC.htm

  30. Thayer KA, Heindel JJ, Bucher JR, Gallo MA. Role of environmental chemicals in diabetes and obesity: a National Toxicology Program workshop review. Environ Health Perspect. 2012;120(6):779–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liu C, Ying Z, Harkema J, Sun Q, Rajagopalan S. Epidemiological and experimental links between air pollution and type 2 diabetes. Toxicol Pathol. 2013;41(2):361–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lee DH, Lee IK, Song K, Steffes M, Toscano W, Baker BA, et al. A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999–2002. Diabetes Care. 2006;29(7):1638–44.

    Article  CAS  PubMed  Google Scholar 

  33. Ruzzin J, Petersen R, Meugnier E, Madsen L, Lock EJ, Lillefosse H, et al. Persistent organic pollutant exposure leads to insulin resistance syndrome. Environ Health Perspect. 2010;118(4):465–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Virtanen MT. Histopathological and ultrastructural changes in the gills of Poeciliareticulatus induced by an organochlorine pesticide. J Environ Pathol Toxicol Oncol. 1986;7:73–85.

    CAS  PubMed  Google Scholar 

  35. Shertzer HG, Genter MB, Shen D, Nebert DW, Chen Y, Dalton TP. TCDD decreases ATP levels and increases reactive oxygen production through changes in mitochondrial F (0) F (1)-ATP synthase and ubiquinone. Toxicol Appl Pharmacol. 2006;217:363–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nakagawa Y, Suzuki T, Ishii H, Ogata A. Biotransformation and cytotoxicity of a brominated flame retardant, tetrabromobisphenol A, and its analogues in rat hepatocytes. Xenobiotica. 2007;37:693–708.

    Article  CAS  PubMed  Google Scholar 

  37. Lind L, Zethelius B, Salihovic S, van Bavel B, Lind PM. Circulating levels of perfluoroalkyl substances and prevalent diabetes in the elderly. Diabetologia. 2014;57(3):473–9.

    Article  CAS  PubMed  Google Scholar 

  38. Esposti MD, Ngo A, Myers MA. Inhibition of mitochondrial complex I may account for IDDM induced by intoxication with the rodenticide Vacor. Diabetes. 1996;45:1531–4.

    Article  CAS  PubMed  Google Scholar 

  39. Rahimi R, Abdollahi MA. review on the mechanism involved in hyperglycaemia induced by organophosphorus pesticides. Pestic Biochem Physiol. 2007;88:115–21.

    Article  CAS  Google Scholar 

  40. Karami-Mohajeri S, Hadian MR, Fouladdel S, Azizi E, Ghahramani MH, Hosseini R, et al. Mechanisms of muscular electrophysiological and mitochondrial dysfunction following exposure tomalathion, an organophosphorus pesticide. Hum ExpToxicol. 2014;33(3):251–63.

    Article  CAS  Google Scholar 

  41. McKinlay R, Plant JA, Bell JNB, Voulvoulis N. Endocrine disrupting pesticides: implications for risk assessment. Environ Int. 2008;34:168–83.

    Article  CAS  PubMed  Google Scholar 

  42. Jeong SH, Kim BY, Kang HG, Ku HK, Cho JH. Effect of chlorpyrifos-methyl on steroid and thyroid hormones in rat F0− andF1-generations. Toxicology. 2006;220:189–202.

    Article  CAS  PubMed  Google Scholar 

  43. Soloman KR, Baker DB, Richards RP, Dixon KR, Klaine SJ. Ecological risk assessment of atrazine in North American surface waters. Environ Toxicol Chem. 1996;15:31–76.

    Article  Google Scholar 

  44. Lim S, Ahn SY, Song IC, Chung MH, Jang HC, Park KS, et al. Chronic exposure to the herbicide, atrazine, causes mitochondrial dysfunction and insulin resistance. PLoS One. 2009;4(4):e5186.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Nicodemo D, Maioli MA, Medeiros HC, Guelfi M, Balieira KV, De Jong D, et al. Fipronil and imidacloprid reduce honeybee mitochondrial activity. Environ Toxicol Chem. 2014;33(9):2070–5.

    Article  CAS  PubMed  Google Scholar 

  46. Lind PM, Zethelius B. Circulating levels of phthalate metabolites are associated with prevalent diabetes in the elderly. Diabetes Care. 2012;35(7):1519–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hurst CH, Waxman DJ. Activation of PPARalpha and PPARgamma by environmental phthalate monoesters. Toxicol Sci. 2003;74:297–308.

    Article  CAS  PubMed  Google Scholar 

  48. Bility MT, Thompson JT, McKee RH, David RM, Butala JH, VandenHeuvel JP. Activation of mouse and human peroxisome proliferator-activated receptors (PPARs) by phthalate monoesters. Toxicol Sci. 2004;82:170.182.

    PubMed  Google Scholar 

  49. Posnack NG, Swift LM, Kay MW, Lee NH, Sarvazyan N. Phthalate exposure changes the metabolic profile of cardiac muscle cells. Environ Health Perspect. 2012;120(9):1243–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ishido M, Suzuki J. Classification of phthalates based on an in vitro neurosphere assay using rat mesencephalic neural stem cells. J Toxicol Sci. 2014;39(1):25–32.

    Article  CAS  PubMed  Google Scholar 

  51. Goodman M, Lakind JS, Mattison DR. Do phthalates act as obesogens in humans? A systematic review of the epidemiological literature. Crit Rev Toxicol. 2014;44(2):151–75.

    Article  CAS  PubMed  Google Scholar 

  52. Polyzos SA, Kountouras J, Deretzi G, Zavos C, Mantzoros CS. The emerging role of endocrine disruptors in pathogenesis of insulin resistance: a concept implicating nonalcoholic fatty liver disease. Curr Mol Med. 2012;12(1):68–82.

    Article  CAS  PubMed  Google Scholar 

  53. Alonso-Magdalena P, Quesada I, Nadal A. Endocrine disruptors in the etiology of type 2 diabetes mellitus. Nat Rev Endocrinol. 2011;7(6):346–53.

    Article  CAS  PubMed  Google Scholar 

  54. Moon MK, Kim MJ, Jung IK, Koo YD, Ann HY, Lee KJ, et al. Bisphenol A impairs mitochondrial function in the liver at doses below the no observed adverse effect level. J Korean Med Sci. 2012;27(6):644–552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kaur K, Chauhan V, Gu F, Chauhan A. Bisphenol A induces oxidative stress and mitochondrial dysfunction in lymphoblasts from children with autism and unaffected siblings. Free Radic Biol Med. 2014;76C:25–33.

    Article  PubMed  Google Scholar 

  56. Chen YW, Yang CY, Huang CF, Hung DZ, Leung YM, Liu SH. Heavy metals and islet function and diabetes development. Islets. 2009;1:169–76.

    Article  PubMed  Google Scholar 

  57. Edwards JR, Prozialeck WC. Cadmium, diabetes and chronic kidney disease. Toxicol Appl Pharmacol. 2009;238:289–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Jomova K, Jenisova Z, Feszterova M, Baros S, Liska J, Hudecova D, et al. Arsenic: toxicity, oxidative stress and human disease. J Appl Toxicol. 2011;31(2):95–107.

    CAS  PubMed  Google Scholar 

  59. Liu C, Ying Z, Harkema J, Sun Q, Rajagopalan S. Epidemiological and experimental links between air pollution and type 2 diabetes. Toxicol Pathol. 2013;41(2):361–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Andersen ZJ, Raaschou-Nielsen O, Ketzel M, Jensen SS, Hvidberg M, Loft S, et al. Diabetes incidence and long-term exposure to air pollution: a cohort study. Diabetes Care. 2012;35(1):92–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Coogan PF, White LF, Jerrett M, Brook RD, Su JG, Seto E, et al. Air pollution and incidence of hypertension and diabetes mellitus in black women living in Los Angeles. Circulation. 2012;125(6):767–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Liu C, Bai Y, Xu X, Sun L, Wang A, Wang TY, et al. Exaggerated effects of particulate matter air pollution in genetic type II diabetes mellitus. Part Fibre Toxicol. 2014; 11:27.

  63. Adar SD, Filigrana PA, Clements N, Peel JL. Ambient Coarse Particulate Matter and Human Health: A Systematic Review and Meta-Analysis. Curr Environ Health Rep. 2014;8(1):258–74.

    Google Scholar 

  64. Lewis W, Day BJ, Copeland WC. Mitochondrial toxicity of NRTI antiviral drugs: an integrated cellular perspective. Nat Rev Drug Discov. 2003;2:812–22.

    Article  CAS  PubMed  Google Scholar 

  65. Gerschenson M, Kim C, Berzins B, Taiwo B, Libutti DE J, Choi J, et al. Mitochondrial function, morphology and metabolic parameters improve after switching from stavudine to a tenofovir-containing regimen. J Antimicrob Chemother. 2009;63:1244–50.

    Article  CAS  PubMed  Google Scholar 

  66. Boelsterli UA, Lim PL. Mitochondrial abnormalities-a link to idiosyncratic drug hepatotoxicity? Toxicol Appl Pharmacol. 2007;220:92–107.

    Article  CAS  PubMed  Google Scholar 

  67. Amacher DE. Drug-associated mitochondrial toxicity and its detection. Curr Med Chem. 2005;12(16):1829–39.

    Article  CAS  PubMed  Google Scholar 

  68. Hectors TL, Vanparys C, Van Gaal LF, Jorens PG, Covaci A, Blust R. Insulin resistance and environmental pollutants: experimental evidence and future perspectives. Environ Health Perspect. 2013;121(11–12):1273–81.

    PubMed  PubMed Central  Google Scholar 

  69. Park WH, Jun DW, Kim JT, Jeong JH, Park H, Chang YS, et al. Novel cell-based assay reveals associations of circulating serum AhR-ligands with metabolic syndrome and mitochondrial dysfunction. Biofactors. 2013;39(4):494–504.

    Article  CAS  PubMed  Google Scholar 

  70. Shanle EK, Xu W. Endocrine disrupting chemicals targeting estrogen receptor signaling: identification and mechanisms of action. Chem Res Toxicol. 2011;24(1):6–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Shizu R, Benoki S, Numakura Y, Kodama S, Miyata M, Yamazoe Y, et al. Xenobiotic-induced hepatocyte proliferation associated with constitutive active/androstane receptor (CAR) or peroxisome proliferator-activated receptor α (PPARα) is enhanced by pregnane X receptor (PXR) activation in mice. PLoS One. 2013;8(4):e61802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Gao J, Xie W. Targeting xenobiotic receptors PXR and CAR for metabolic diseases. Trends Pharmacol Sci. 2012;33(10):552–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Pereira-Fernandes A, Demaegdt H, Vandermeiren K, Hectors TL, Jorens PG, Blust R, et al. Evaluation of screening system for obesogenic compounds: screening of endocrinedisrupting compounds and evaluation of the PPAR dependency of the effect. PLoS One. 2013;8(10):e77481.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Patel CJ, Bhattacharya J, Butte AJ. An Environment-Wide Association Study (EWAS) on type 2 diabetes mellitus. PLoS One. 2010;5(5):e10746.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Kim JT, Kim SS, Jun DW, Hwang YH, Park WH, Pak YK, et al. Serum arylhydrocarbon receptor transactivating activity is elevated in type 2 diabetic patients with diabetic nephropathy. J Diabetes Investig. 2013;4(5):483–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported in part by MIC & IITA through the IT Leading R & D Support Project.

Conflict of interest statement

Disclosure: The authors do not have any financial relationship with organizations. Dr. HK Lee owns a part of patent (PCT/KR2011/006583) for the application of cell based arylhydrocarbon receptor ligands assay to the diagnosis of metabolic syndrome. The authors have full control of all primary data and that we agree to allow the journal to review our data if requested.

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  1. Department of Internal Medicine, College of Medicine, Eulji University, Seoul, South Korea

    Jin Taek Kim & Hong Kyu Lee

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Kim, J.T., Lee, H.K. Metabolic syndrome and the environmental pollutants from mitochondrial perspectives. Rev Endocr Metab Disord 15, 253–262 (2014). https://doi.org/10.1007/s11154-014-9297-5

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