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Obesity and diabetes: from genetics to epigenetics

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Abstract

Obesity is becoming an epidemic health problem. During the last years not only genetic but also, and primarily, environmental factors have been supposed to contribute to the susceptibility to weight gain or to develop complications such as type 2 diabetes. In spite of the intense efforts to identify genetic predisposing variants, progress has been slow and success limited, and the common obesity susceptibility variants identified only explains a small part of the individual variation in risk. Moreover, there is evidence that the current epidemic of obesity and diabetes is environment-driven. Recent studies indicate that normal metabolic regulation during adulthood besides requiring a good balance between energy intake and energy expenditure, can be also affected by pre- and post-natal environments. In fact, maternal nutritional constraint during pregnancy can alter the metabolic phenotype of the offspring by means of epigenetic regulation of specific genes, and this can be passed to the next generations. Studies focused on epigenetic marks in obesity found altered methylation and/or histone acetylation levels in genes involved in specific but also in more general metabolic processes. Recent researches point out the continuous increase of “obesogens”, in the environment and food chains, above all endocrine disruptors, chemicals that interfere with many homeostatic mechanisms. Taken into account the already existing data on the effects of obesogens, and the multiple potential targets with which they might interfere daily, it seems likely that the exposure to obesogens can have an important role in the obesity and diabesity pandemic.

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References

  1. Global status report on non communicable diseases 2010 Chapter 1. Burden: mortality, morbidity and risk factors World Health Organization 2011 ISBN 978 92 4 156422 9 ISBN 978 92 4 068645 8. http://www.who.int/nmh/publications/ncd_report_full_en.pdf

  2. Kelly T, Yang W, Chen CS, Reynolds K, He J (2008) Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond) 32:1431–1437. doi:10.1038/ijo.2008.102

    CAS  Google Scholar 

  3. Wang Y, Lobstein T (2006) Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 1:11–25

    PubMed  Google Scholar 

  4. Bell AC, Ge K, Popkin BM (2001) Weight gain and its predictors in Chinese adults. Int J Obes Relat Metab Disord 25:1079–1086

    CAS  PubMed  Google Scholar 

  5. Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zhao Z, Li Q, Zhou Z, Shan G, He J, China National Diabetes and Metabolic Disorders Study Group (2010) China National Diabetes and Metabolic Disorders Study Group. Prevalence of diabetes among men and women in China. N Engl J Med 362:1090–1110. doi:10.1056/NEJMoa0908292

    CAS  PubMed  Google Scholar 

  6. Bornstein SR, Ehrhart-Bornstein M, Wong ML, Licinio J (2008) Is the worldwide epidemic of obesity a communicable feature of globalization? Exp Clin Endocrinol Diabetes 116:S30–S32. doi:10.1055/s-2008-1081485

    CAS  PubMed  Google Scholar 

  7. Bartolomucci A, Parmigiani S, Rodgers RJ, Vidal-Puig A, Allan SE, Siegel V (2012) The Obese Species: a special issue on obesity and metabolic disorders foreword. Dis Model Mech 5:563–564. doi:10.1242/dmm.010611

    PubMed  PubMed Central  Google Scholar 

  8. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS (2003) Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 289:76–79

    PubMed  Google Scholar 

  9. Irigaray P, Newby JA, Lacomme S, Belpomme D (2007) Overweight/obesity and cancer genesis: more than a biological link. Biomed Pharmacother 61:665–678

    CAS  PubMed  Google Scholar 

  10. Berger NA (2014) Obesity and cancer pathogenesis. Ann N Y Acad Sci 1311:57–76

    CAS  PubMed  Google Scholar 

  11. Lopez KN, Knudson JD (2012) Obesity: from the agricultural revolution to the contemporary pediatric epidemic. Congenit Heart Dis 7:189–199. doi:10.1111/j.1747-0803.2011.00618

    PubMed  Google Scholar 

  12. Speakman JR, O’Rahilly S (2012) Fat: an evolving issue. Dis Model Mech 5:569–573. doi:10.1242/dmm.010553

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Schaffler A, Muller-Ladner U, Scholmerich J, Buchler C (2006) Role of adipose tissue as an inflammatory organ in human diseases. Endocr Rev 27:449–467

    CAS  PubMed  Google Scholar 

  14. DeBoer MD (2013) Obesity, systemic inflammation, and increased risk for cardiovascular disease and diabetes among adolescents: a need for screening tools to target interventions. Nutrition 29:379–386. doi:10.1016/j.nut.2012.07.003

    PubMed  PubMed Central  Google Scholar 

  15. Murphy KG, Bloom SR (2006) Gut hormones and the regulation of energy homeostasis. Nature 444(7121):854–859

    CAS  PubMed  Google Scholar 

  16. Grün F, Blumberg B (2009) Minireview: The Case for Obesogens. Mol Endocrinol 23:1127–1134. doi:10.1210/me.2008-0485

    PubMed  PubMed Central  Google Scholar 

  17. Jo J, Gavrilova O, Pack S, Jou W, Mullen S, Sumner AE, Cushman SW, Periwal V (2009) Hypertrophy and/or Hyperplasia: Dynamics of Adipose Tissue Growth. PLoS Comput Biol 5:e1000324. doi:10.1371/journal.pcbi.1000324

    PubMed  PubMed Central  Google Scholar 

  18. Grün F, Blumberg B (2009) Endocrine disrupters as obesogens. Mol Cell Endocrinol 304:19–29. doi:10.1016/j.mce.2009.02.018

    PubMed  PubMed Central  Google Scholar 

  19. Permutt MA, Wasson J, Cox N (2005) Genetic epidemiology of diabetes. J Clin Invest 115:1431–1439

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Herskind AM, McGue M, Iachine IA, Holm N, Sørensen TI, Harvald B, Vaupel JW (1996) Untangling genetic influences on smoking, body mass index and longevity: a multivariate study of 2464 Danish twins followed for 28 years. Hum Genet 98:467–475

    CAS  PubMed  Google Scholar 

  21. Rice T, Pérusse L, Bouchard C, Rao DC (1999) Familial aggregation of body mass index and subcutaneous fat measures in the longitudinal Québec family study. Genet Epidemiol 16:316–334

    CAS  PubMed  Google Scholar 

  22. Stunkard AJ, Foch TT, Hrubec Z (1986) A twin study of human obesity. J Am Med Assoc 256:51–54

    CAS  Google Scholar 

  23. Stunkard AJ, Sørensen TI, Hanis C, Teasdale TW, Chakraborty R, Schull WJ, Schulsinger F (1986) An adoption study of human obesity. N Engl J Med 314:193–198

    CAS  PubMed  Google Scholar 

  24. Poulsen P, Kyvik KO, Vaag A, Beck-Nielsen H (1999) Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance–a population-based twin study. Diabetologia 42:139–145

    CAS  PubMed  Google Scholar 

  25. Köbberling J, Tillil (1982) Empirical risk figures for first degree relatives of non-insulin dependent diabetics. In: Köbberling J, Tattersall R (eds) The Genetics of Diabetes Mellitus. Academic Press, London

    Google Scholar 

  26. Groop L, Pociot F (2014) Genetics of diabetes––are we missing the genes or the disease? Mol Cell Endocrinol 382:726–739. doi:10.1016/j.mce.2013.04.002

    CAS  PubMed  Google Scholar 

  27. Newbold RR, Padilla-Banks E, Jefferson WN (2009) Environmental estrogens and obesity. Mol Cell Endocrinol 304(1–2):84–89. doi:10.1016/j.mce.2009.02.024

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372(6505):425–432

    CAS  PubMed  Google Scholar 

  29. Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556. doi:10.1210/jc.2004-0395

    CAS  PubMed  Google Scholar 

  30. Collins S (2005) Overview of clinical perspectives and mechanisms of obesity. Birth Defects Res A Clin Mol Teratol 73:470–471

    CAS  PubMed  Google Scholar 

  31. Shimizu H, Inoue K, Mori M (2007) The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure. J Endocrinol 193:1–9

    CAS  PubMed  Google Scholar 

  32. Loos RJ (2012) Genetic determinants of common obesity and their value in prediction. Best Pract Res Clin Endocrinol Metab 26:211–226. doi:10.1016/j.beem.2011.11.003

    CAS  PubMed  Google Scholar 

  33. D’Angelo CS, Koiffmann CP (2012) Copy number variants in obesity-related syndromes: review and perspectives on novel molecular approaches. J Obes 2012:845480. doi:10.1155/2012/845480

    PubMed  PubMed Central  Google Scholar 

  34. Frayling TM (2007) Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genet 8:657–662

    CAS  PubMed  Google Scholar 

  35. Fall T, Ingelsson E (2014) Genome-wide association studies of obesity and metabolic syndrome. Mol Cell Endocrinol 382:740–757. doi:10.1016/j.mce.2012.08.018

    CAS  PubMed  Google Scholar 

  36. Schmid PM, Heid I, Buechler C, Steege A, Resch M, Birner C, Endemann DH, Riegger GA, Luchner A (2012) Expression of fourteen novel obesity-related genes in Zucker diabetic fatty rats. Cardiovasc Diabetol 11:48. doi:10.1186/1475-2840-11-48

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Kwan T, Benovoy D, Dias C, Gurd S, Provencher C, Beaulieu P, Hudson TJ, Sladek R, Majewski J (2008) Genome-wide analysis of transcript isoform variation in humans. Nat Genet 40:225–231. doi:10.1038/ng.2007.57

    CAS  PubMed  Google Scholar 

  38. Bachmann-Gagescu R, Mefford HC, Cowan C, Glew GM, Hing AV, Wallace S, Bader PI, Hamati A, Reitnauer PJ, Smith R, Stockton DW, Muhle H, Helbig I, Eichler EE, Ballif BC, Rosenfeld J, Tsuchiya KD (2010) Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity. Genet Med 12:641–647. doi:10.1097/GIM.0b013e3181ef4286

    PubMed  Google Scholar 

  39. Glessner JT, Bradfield JP, Wang K, Takahashi N, Zhang H, Sleiman PM, Mentch FD, Kim CE, Hou C, Thomas KA, Garris ML, Deliard S, Frackelton EC, Otieno FG, Zhao J, Chiavacci RM, Li M, Buxbaum JD, Berkowitz RI, Hakonarson H, Grant SF (2010) A genome-wide study reveals copy number variants exclusive to childhood obesity cases. Am J Hum Genet 87:661–666. doi:10.1016/j.ajhg.2010.09.014

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Drong AW, Lindgren CM, McCarthy MI (2012) The genetic and epigenetic basis of type 2 diabetes and obesity. Clin Pharmacol Ther 92:707–715. doi:10.1038/clpt.2012.149

    CAS  PubMed  Google Scholar 

  41. Schwenk RW, Vogel H, Schürmann A (2013) Genetic and epigenetic control of metabolic health. Mol Metab 2:337–347

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Xia Q, Grant SF (2013) The genetics of human obesity. Ann N Y Acad Sci 1281:178–190. doi:10.1111/nyas.12020

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Choquet H, Meyre D (2011) Molecular basis of obesity: current status and future prospects. Curr Genomics 12:154–168. doi:10.2174/138920211795677921

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM et al (2009) Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 41:25–34. doi:10.1038/ng.287

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU et al (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 42:937–948. doi:10.1038/ng.686

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, Cardon LR, Chakravarti A, Cho JH, Guttmacher AE, Kong A, Kruglyak L, Mardis E, Rotimi CN, Slatkin M, Valle D, Whittemore AS, Boehnke M, Clark AG, Eichler EE, Gibson G, Haines JL, Mackay TF, McCarroll SA, Visscher PM (2009) Finding the missing heritability of complex diseases. Nature 461(7265):747–753. doi:10.1038/nature08494

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Jones V (2006) The “Diabesity” epidemic: let’s rehabilitate America. Med Gen Med 8:34

    Google Scholar 

  48. Gluckman P, Hanson M (2004) Developmental origins of disease paradigm: a mechanistic and evolutionary perspective. Pediatr Res 56:311–317

    PubMed  Google Scholar 

  49. Neel JV (1999) Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? 1962. Bull World Health Organ 77:694–703 discussion 692-3

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Baschetti R (1998) Diabetes epidemic in newly westernized populations: is it due to thrifty genes or to genetically unknown foods? J R Soc Med 91:622–625

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Speakman JR (2007) A nonadaptive scenario explaining the genetic predisposition to obesity: the “predation release” hypothesis. Cell Metab 6:5–12

    CAS  PubMed  Google Scholar 

  52. Hales CN, Barker DJ (2001) The thrifty phenotype hypothesis. Br Med Bull 60:5–20. doi:10.1093/bmb/60.1.5

    CAS  PubMed  Google Scholar 

  53. Watve MG, Yajnik CS (2007) Evolutionary origins of insulin resistance: a behavioral switch hypothesis. BMC Evol Biol 7:61. doi:10.1186/1471-2148-7-61

    PubMed  PubMed Central  Google Scholar 

  54. Lucas A (1991) Programming by early nutrition in man. Ciba Found Symp 156:38–50 discussion 50-5

    CAS  PubMed  Google Scholar 

  55. Hales CN, Barker DJ, Clark PM, Cox LJ, Fall C, Osmond C, Winter PD (1991) Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 303(6809):1019–1022

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  57. Michels KB, Trichopoulos D, Robins JM, Rosner BA, Manson JE, Hunter DJ, Colditz GA, Hankinson SE, Speizer FE, Willett WC (1996) Birthweight as a risk factor for breast cancer. Lancet 348(9041):1542–1546

    CAS  PubMed  Google Scholar 

  58. Keller G, Zimmer G, Mall G, Ritz E, Amann K (2003) Nephron number in patients with primary hypertension. N Engl J Med 348:101–108

    PubMed  Google Scholar 

  59. Hallan S, Euser AM, Irgens LM, Finken MJ, Holmen J, Dekker FW (2008) Effect of intrauterine growth restriction on kidney function at young adult age: the Nord Trøndelag Health (HUNT 2) Study. Am J Kidney Dis 51:10–20

    PubMed  Google Scholar 

  60. Barker DJ (1995) Fetal origins of coronary heart disease. BMJ 311(6998):171–174

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Barker DJ (1996) The fetal origins of hypertension. J Hypertens Suppl 14:S117–S120

    CAS  PubMed  Google Scholar 

  62. Warner JA, Jones AC, Miles EA, Colwell BM, Warner JO (1997) Prenatal origins of asthma and allergy. Ciba Found Symp 206:220–228 discussion 228-32

    CAS  PubMed  Google Scholar 

  63. Warner JA, Jones CA, Jones AC, Warner JO (2000) Prenatal origins of allergic disease. J Allergy Clin Immunol 105:S493–S498

    CAS  PubMed  Google Scholar 

  64. Harris GW (1964) Sex hormones, brain development and brain function. Endocrinology 75:627–648

    CAS  PubMed  Google Scholar 

  65. Ehrhardt AA, Meyer-Bahlburg HF (1979) Prenatal sex hormones and the developing brain: effects on psychosexual differentiation and cognitive function. Annu Rev Med 30:417–430

    CAS  PubMed  Google Scholar 

  66. Gluckman PD, Cutfield W, Hofman P, Hanson MA (2005) The fetal, neonatal, and infant environments – the long-term consequences for disease risk. Early Hum Dev 81:51–59

    PubMed  Google Scholar 

  67. Gluckman PD, Hanson MA (2006) The conceptual basis for the developmental origins of health and disease. In: GluckmanP HansonM (ed) developmental origins of health and disease. Cambridge University Press, Cambridge, pp 33–50

    Google Scholar 

  68. Roseboom TJ, van der Meulen JH, Ravelli AC, Osmond C, Barker DJ, Bleker OP (2001) Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Mol Cell Endocrinol 185:93–98

    CAS  PubMed  Google Scholar 

  69. Painter RC, Roseboom TJ, Bleker OP (2005) Prenatal exposure to the Dutch famine and disease in later life: an overview. Reprod Toxicol 20:345–352

    CAS  PubMed  Google Scholar 

  70. Roseboom TJ, van der Meulen JH, Osmond C, Barker DJ, Ravelli AC, Bleker OP (2000) Plasma lipid profiles in adults after prenatal exposure to the Dutch famine. Am J Clin Nutr 72:1101–1106

    CAS  PubMed  Google Scholar 

  71. Stein AD, Zybert PA, van der Pal-de Bruin K, Lumey LH (2006) Exposure to famine during gestation, size at birth, and blood pressure at age 59 y: evidence from the Dutch Famine. Eur J Epidemiol 21:759–765

    PubMed  Google Scholar 

  72. Roseboom TJ, van der Meulen JH, Osmond C, Barker DJ, Ravelli AC, Schroeder-Tanka JM, van Montfrans GA, Michels RP, Bleker OP (2000) Coronary heart disease after prenatal exposure to the Dutch famine, 1944-45. Heart 84:595–598

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Roseboom TJ, Van Der Meulen JH, Ravelli AC, Osmond C, Barker DJ, Bleker OP (2003) Perceived health of adults after prenatal exposure to the Dutch famine. Paediatr Perinat Epidemiol 17:391–397

    PubMed  Google Scholar 

  74. Kyle UG, Pichard C (2006) The Dutch Famine of 1944-1945: a pathophysiological model of long-term consequences of wasting disease. Curr Opin Clin Nutr Metab Care 9:388–394

    PubMed  Google Scholar 

  75. Painter RC, Osmond C, Gluckman P, Hanson M, Phillips DI, Roseboom TJ (2008) Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life. BJOG 115:1243–1249. doi:10.1111/j.1471-0528.2008.01822.x

    CAS  PubMed  Google Scholar 

  76. Stanner SA, Bulmer K, Andrès C, Lantseva OE, Borodina V, Poteen VV, Yudkin JS (1997) Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study. BMJ 315(7119):1342–1348

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Bell C (2004) Long term mortality after starvation during the Leningrad siege: no evidence that starvation around puberty causes later cardiovascular disease. BMJ 328:346

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Gluckman PD, Hanson MA (2004) Living with the past: evolution, development, and patterns of disease. Science 305:1733–1736

    CAS  PubMed  Google Scholar 

  79. Fisher RE, Steele M, Karrow NA (2012) Fetal programming of the neuroendocrine-immune system and metabolic disease. J Pregnancy 2012:792934. doi:10.1155/2012/792934

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Huang JS, Lee TA, Lu MC (2007) Prenatal programming of childhood overweight and obesity. Matern Child Health J 11:461–473

    PubMed  Google Scholar 

  81. Sookoian S, Gianotti TF, Burgueño AL, Pirola CJ (2013) Fetal metabolic programming and epigenetic modifications: a systems biology approach. Pediatr Res 73(4 Pt 2):531–542. doi:10.1038/pr.2013.2

    CAS  PubMed  Google Scholar 

  82. Lukaszewski MA, Eberlé D, Vieau D, Breton C (2013) Nutritional manipulations in the perinatal period program adipose tissue in offspring. Am J Physiol Endocrinol Metab 305:E1195–E1207. doi:10.1152/ajpendo.00231.2013

    CAS  PubMed  Google Scholar 

  83. Martínez JA, Cordero P, Campión J, Milagro FI (2012) Interplay of early-life nutritional programming on obesity, inflammation and epigenetic outcomes. Proc Nutr Soc 71:276–283. doi:10.1017/S0029665112000055

    PubMed  Google Scholar 

  84. Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, Rodford J, Slater-Jefferies JL, Garratt E, Crozier SR, Emerald BS, Gale CR, Inskip HM, Cooper C, Hanson MA (2011) Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes 60:1528–1534. doi:10.2337/db10-0979

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Li CC, Young PE, Maloney CA, Eaton SA, Cowley MJ, Buckland ME, Preiss T, Henstridge DC, Cooney GJ, Febbraio MA, Martin DI, Cropley JE, Suter CM (2013) Maternal obesity and diabetes induces latent metabolic defects and widespread epigenetic changes in isogenic mice. Epigenetics 8:602–611. doi:10.4161/epi.24656

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Milagro FI, Mansego ML, De Miguel C, Martínez JA (2013) Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives. Mol Asp Med 34:782–812. doi:10.1016/j.mam.2012.06.010

    CAS  Google Scholar 

  87. Moleres A, Campión J, Milagro FI, Marcos A, Campoy C, Garagorri JM, Gómez-Martínez S, Martínez JA, Azcona-Sanjulián MC, Martí A, EVASYON Study Group (2013) Differential DNA methylation patterns between high and low responders to a weight loss intervention in overweight or obese adolescents: the EVASYON study. FASEB J 27:2504–2512. doi:10.1096/fj.12-215566

    CAS  PubMed  Google Scholar 

  88. Soubry A, Murphy SK, Wang F, Huang Z, Vidal AC, Fuemmeler BF, Kurtzberg J, Murtha A, Jirtle RL, Schildkraut JM, Hoyo C (2013) Newborns of obese parents have altered DNA methylation patterns at imprinted genes. Int J Obes (Lond). doi:10.1038/ijo.2013.193

  89. Ge ZJ, Luo SM, Lin F, Liang QX, Huang L, Wei YC, Hou Y, Han ZM, Schatten H, Sun QY (2014) DNA methylation in oocytes and liver of female mice and their offspring: effects of high-fat-diet-induced obesity. Environ Health Perspect 122:159–164. doi:10.1289/ehp.1307047

    PubMed  PubMed Central  Google Scholar 

  90. Vidal AC, Murphy SK, Murtha AP, Schildkraut JM, Soubry A, Huang Z, Neelon SE, Fuemmeler B, Iversen E, Wang F, Kurtzberg J, Jirtle RL, Hoyo C (2013) Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring. Int J Obes (Lond) 37:907–913. doi:10.1038/ijo.2013.47

    CAS  Google Scholar 

  91. Crujeiras AB, Campion J, Díaz-Lagares A, Milagro FI, Goyenechea E, Abete I, Casanueva FF, Martínez JA (2013) Association of weight regain with specific methylation levels in the NPY and POMC promoters in leukocytes of obese men: a translational study. Regul Pept 186:1–6. doi:10.1016/j.regpep.2013.06.012

    CAS  PubMed  Google Scholar 

  92. Lesseur C, Armstrong DA, Paquette AG, Koestler DC, Padbury JF, Marsit CJ (2013) Tissue-specific Leptin promoter DNA methylation is associated with maternal and infant perinatal factors. Mol Cell Endocrinol 381:160–167. doi:10.1016/j.mce.2013.07.024

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Rönn T, Volkov P, Davegårdh C, Dayeh T, Hall E, Olsson AH, Nilsson E, Tornberg A, Dekker Nitert M, Eriksson KF, Jones HA, Groop L, Ling C (2013) A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet 9:e1003572. doi:10.1371/journal.pgen.1003572

    PubMed  PubMed Central  Google Scholar 

  94. Wang X, Lacza Z, Sun YE, Han W (2014) Leptin resistance and obesity in mice with deletion of methyl-CpG-binding protein 2 (MeCP2) in hypothalamic pro-opiomelanocortin (POMC) neurons. Diabetologia 57:236–245

    CAS  PubMed  Google Scholar 

  95. Baillie-Hamilton PF (2002) Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med 8:185–192

    PubMed  Google Scholar 

  96. Grün F, Blumberg B (2006) Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology 147:S50–S55

    PubMed  Google Scholar 

  97. Grün F (2010) Obesogens. Curr Opin Endocrinol Diabetes Obes 17:453–459. doi:10.1097/MED.0b013e32833ddea0

    PubMed  Google Scholar 

  98. Grün F, Blumberg B (2007) Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis. Rev Endocr Metab Disord 8:161–171

    PubMed  Google Scholar 

  99. Somm E, Schwitzgebel VM, Toulotte A, Cederroth CR, Combescure C, Nef S, Aubert ML, Hüppi PS (2009) Perinatal exposure to bisphenol a alters early adipogenesis in the rat. Environ Health Perspect 117:1549–1555. doi:10.1289/ehp.11342

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Kirchner S, Kieu T, Chow C, Casey S, Blumberg B (2010) Prenatal Exposure to the Environmental Obesogen Tributyltin Predisposes Multipotent Stem Cells to Become Adipocytes. Mol Endocrinol 24:526–539. doi:10.1210/me.2009-0261

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR Jr, Lee DH, Shioda T, Soto AM, vom Saal FS, Welshons WV, Zoeller RT, Myers JP (2012) Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev 33:378–455. doi:10.1210/er.2011-1050

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Power C, Jefferis BJ (2002) Fetal environment and subsequent obesity: a study of maternal smoking. Int J Epidemiol 31:413–419

    PubMed  Google Scholar 

  103. Dolinoy DC (2008) The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr Rev 66:S7–S11. doi:10.1111/j.1753-4887.2008.00056.x

    PubMed  PubMed Central  Google Scholar 

  104. Fleisch AF, Wright RO, Baccarelli AA (2012) Environmental epigenetics: a role in endocrine disease? J Mol Endocrinol 49:R61–R67. doi:10.1530/JME-12-0066

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Zoeller RT (2007) Environmental chemicals impacting the thyroid: targets and consequences. Thyroid 17:811–817

    CAS  PubMed  Google Scholar 

  106. Knudsen N, Laurberg P, Rasmussen LB, Bülow I, Perrild H, Ovesen L, Jørgensen T (2005) Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab 90:4019–4024

    CAS  PubMed  Google Scholar 

  107. Tracey R, Manikkam M, Guerrero-Bosagna C, Skinner MK (2013) Hydrocarbons (jet fuel JP-8) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. Reprod Toxicol 36:104–116. doi:10.1016/j.reprotox.2012.11.011

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK (2013) Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS One 8:e55387. doi:10.1371/journal.pone.0055387

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Elobeid MA, Allison DB (2008) Putative environmental-endocrine disruptors and obesity: a review. Curr Opin Endocrinol Diabetes Obes 15:403–408. doi:10.1097/MED.0b013e32830ce95c

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Irigaray P, Lacomme S, Mejean L, Belpomme D (2009) Ex vivo study of incorporation into adipocytes and lipolysis-inhibition effect of polycyclic aromatic hydrocarbons. Toxicol Lett 187:35–39. doi:10.1016/j.toxlet.2009.01.021

    CAS  PubMed  Google Scholar 

  111. Irigaray P, Belpomme D (2010) Basic properties and molecular mechanisms of exogenous chemical carcinogens. Carcinogenesis 31:135–148

    CAS  PubMed  Google Scholar 

  112. Neel BA, Sargis RM (2011) The Paradox of Progress: environmental disruption of metabolism and the diabetes epidemic. Diabetes 60:1838–1848

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Jørgensen ME, Borch-Johnsen K, Bjerregaard P (2008) A cross-sectional study of the association between persistent organic pollutants and glucose intolerance among Greenland Inuit. Diabetologia 51:1416–1422

    PubMed  Google Scholar 

  114. Lai MS, Hsueh YM, Chen CJ, Shyu MP, Chen SY, Kuo TL, Wu MM, Tai TY (1994) Ingested inorganic arsenic and prevalence of diabetes mellitus. Am J Epidemiol 139:484–492

    CAS  PubMed  Google Scholar 

  115. Ukropec J, Radikova Z, Huckova M, Koska J, Kocan A, Sebokova E, Drobna B, Trnovec T, Susienkova K, Labudova V, Gasperikova D, Langer P, Klimes I (2010) High prevalence of prediabetes and diabetes in a population exposed to high levels of an organochlorine cocktail. Diabetologia 53:899–906. doi:10.1007/s00125

    CAS  PubMed  Google Scholar 

  116. Lim JS, Lee DH, Jacobs DR Jr (2008) Association of brominated flame retardants with diabetes and metabolic syndrome in the U.S. population, 2003-2004. Diabetes Care 31:1802–1807. doi:10.2337/dc08-0850

    PubMed  PubMed Central  Google Scholar 

  117. Stahlhut RW, van Wijngaarden E, Dye TD, Cook S, Swan SH (2007) Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males. Environ Health Perspect 115:876–882

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Henriksen GL, Ketchum NS, Michalek JE, Swaby JA (1997) Serum dioxin and diabetes mellitus in veterans of operation ranch hand. Epidemiology 8:252–258

    CAS  PubMed  Google Scholar 

  119. Bertazzi PA, Consonni D, Bachetti S, Rubagotti M, Baccarelli A, Zocchetti C, Pesatori AC (2001) Health effects of dioxin exposure: a 20-year mortality study. Am J Epidemiol 153:1031–1044

    CAS  PubMed  Google Scholar 

  120. Wang SL, Tsai PC, Yang CY, Leon Guo Y (2008) Increased risk of diabetes and polychlorinated biphenyls and dioxins: a 24-year follow-up study of the Yucheng cohort. Diabetes Care 31:1574–1579

    PubMed  PubMed Central  Google Scholar 

  121. Beard J, Sladden T, Morgan G, Berry G, Brooks L, McMichael A (2003) Health impacts of pesticide exposure in a cohort of outdoor workers. Environ Health Perspect 111:724–730

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Calvert GM, Sweeney MH, Deddens J, Wall DK (1999) Evaluation of diabetes mellitus, serum glucose, and thyroid function among United States workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Occup Environ Med 56:270–276

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Lang IA, Galloway TS, Scarlett A, Henley WE, Depledge M, Wallace RB, Melzer D (2008) Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA 300:1303–1310. doi:10.1001/jama.300.11.1303

    CAS  PubMed  Google Scholar 

  124. Lee DH, Lee IK, Song K, Steffes M, Toscano W, Baker BA, Jacobs DR Jr (2006) 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 29:1638–1644

    CAS  PubMed  Google Scholar 

  125. Alonso-Magdalena P, Ropero AB, Soriano S, Quesada I, Nadal A (2010) Bisphenol-A: a new diabetogenic factor? Hormones (Athens) 9:118–126

    Google Scholar 

  126. Gayathri NS, Dhanya CR, Indu AR, Kurup PA (2004) Changes in some hormones by low doses of di (2-ethyl hexyl) phthalate (DEHP), a commonly used plasticizer in PVC blood storage bags & medical tubing. Indian J Med Res 119:139–144

    CAS  PubMed  Google Scholar 

  127. Remillard RB, Bunce NJ (2002) Linking dioxins to diabetes: epidemiology and biologic plausibility. Environ Health Perspect 110:853–858

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Hoppe AA, Carey GB (2007) Polybrominated diphenyl ethers as endocrine disruptors of adipocyte metabolism. Obesity (Silver Spring) 15:2942–2950

    CAS  Google Scholar 

  129. Ling C, Groop L (2009) Epigenetics: a molecular link between environmental factors and type 2 diabetes. Diabetes 58:2718–2725

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 328(5979):690

    Google Scholar 

  131. Anway MD, Skinner MK (2006) Epigenetic transgenerational actions of endocrine disruptors. Endocrinology 147(6 Suppl):S43–S49

    CAS  PubMed  Google Scholar 

  132. Anway MD, Leathers C, Skinner MK (2006) Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology 147:5515–5523

    CAS  PubMed  Google Scholar 

  133. Taubes G (2009) Insulin resistance. Prosperity’s plague. Science 325:256–260. doi:10.1126/science.325_256

    CAS  PubMed  Google Scholar 

  134. Petersen KF, Shulman GI (2006) Etiology of insulin resistance. Am J Med 119:S10–S16

    PubMed  PubMed Central  Google Scholar 

  135. Hotamisligil GS (2010) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140:900–917. doi:10.1016/j.cell.2010.02.034

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–445. doi:10.1146/annurev-immunol-031210-101322

    CAS  PubMed  Google Scholar 

  137. Heilbronn LK, Campbell LV (2008) Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity. Curr Pharm Des 14:1225–1230

    CAS  PubMed  Google Scholar 

  138. Verdam FJ, Fuentes S, de Jonge C, Zoetendal EG, Erbil R, Greve JW, Buurman WA, de Vos WM, Rensen SS (2013) Human intestinal microbiota composition is associated with local and systemic inflammation in obesity. Obesity (Silver Spring) 21:E607–E615. doi:10.1002/oby.20466

    CAS  Google Scholar 

  139. Musso G, Gambino R, Cassader M (2010) Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care 33:2277–2284. doi:10.2337/dc10-0556

    PubMed  PubMed Central  Google Scholar 

  140. Xu J, Gordon JI (2003) Inaugural Article: honor thy symbionts. Proc Natl Acad Sci USA 100:10452–10459

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444:1022–1023

    CAS  PubMed  Google Scholar 

  142. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA 107:11971–11975. doi:10.1073/pnas.1002601107

    PubMed  PubMed Central  Google Scholar 

  143. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO (2007) Development of the human infant intestinal microbiota. PLoS Biol 5:e177

    PubMed  PubMed Central  Google Scholar 

  144. Claesson MJ, Cusack S, O’Sullivan O, Greene-Diniz R, de Weerd H, Flannery E, Marchesi JR, Falush D, Dinan T, Fitzgerald G, Stanton C, van Sinderen D, O’Connor M, Harnedy N, O’Connor K, Henry C, O’Mahony D, Fitzgerald AP, Shanahan F, Twomey C, Hill C, Ross RP, O’Toole PW (2011) Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci USA 108:4586–4591. doi:10.1073/pnas.1000097107

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Tsai F, Coyle WJ (2009) The microbiome and obesity: is obesity linked to our gut flora? Curr Gastroenterol Rep 11:307–313

    PubMed  Google Scholar 

  146. Ley RE (2010) Obesity and the human microbiome. Curr Opin Gastroenterol 26:5–11. doi:10.1097/MOG.0b013e328333d751

    PubMed  Google Scholar 

  147. Shen J, Obin MS, Zhao L (2013) The gut microbiota, obesity and insulin resistance. Mol Asp Med 34:39–58

    CAS  Google Scholar 

  148. Zeigler CC, Persson GR, Wondimu B, Marcus C, Sobko T, Modéer T (2012) Microbiota in the oral subgingival biofilm is associated with obesity in adolescence. Obesity (Silver Spring) 20:157–164

    CAS  Google Scholar 

  149. DiBaise JK, Zhang H, Crowell MD, Krajmalnik-Brown R, Decker GA, Rittmann BE (2008) Gut microbiota and its possible relationship with obesity. Mayo Clin Proc 83:460–469

    PubMed  Google Scholar 

  150. Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A 104:979–984

    PubMed  PubMed Central  Google Scholar 

  151. Greiner T, Bäckhed F (2011) Effects of the gut microbiota on obesity and glucose homeostasis. Trends Endocrinol Metab 22:117–123

    CAS  PubMed  Google Scholar 

  152. Dumas ME, Barton RH, Toye A, Cloarec O, Blancher C, Rothwell A, Fearnside J, Tatoud R, Blanc V, Lindon JC, Mitchell SC, Holmes E, McCarthy MI, Scott J, Gauguier D, Nicholson JK (2006) Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc Natl Acad Sci USA 103:12511–12516

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Ghanim H, Abuaysheh S, Sia CL, Korzeniewski K, Chaudhuri A, Fernandez-Real JM, Dandona P (2009) Increase in plasma endotoxin concentrations and the expression of toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care 32:2281–2287

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Snedeker SM, Hay AG (2012) Do interactions between gut ecology and environmental chemicals contribute to obesity and diabetes? Environ Health Perspect 120:332–339

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Remely M, Aumueller E, Merold C, Dworzak S, Hippe B, Zanner J, Pointner A, Brath H, Haslberger AG (2014) Effects of short chain fatty acid producing bacteria on epigenetic regulation of FFAR3 in type 2 diabetes and obesity. Gene 537:85–92. doi:10.1016/j.gene.2013.11.081

    CAS  PubMed  Google Scholar 

  156. Skinner MK (2007) Endocrine disruptors and epigenetic transgenerational disease etiology. Pediatr Res 61:48R–50R

    CAS  PubMed  Google Scholar 

  157. Kaati G, Bygren LO, Edvinsson S (2002) Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet 10:682–688

    CAS  PubMed  Google Scholar 

  158. Kaati G, Bygren LO, Pembrey M, Sjöström M (2007) Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet 15:784–790

    CAS  PubMed  Google Scholar 

  159. Plagemann A (2005) Perinatal programming and functional teratogenesis: impact on body weight regulation and obesity. Physiol Behav 86:661–668

    CAS  PubMed  Google Scholar 

  160. Chang GQ, Gaysinskaya V, Karatayev O, Leibowitz SF (2008) Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity. J Neurosci 28:12107–12119. doi:10.1523/JNEUROSCI.2642-08.2008

    CAS  PubMed  PubMed Central  Google Scholar 

  161. De Ferranti SD, Osganian SK (2007) Epidemiology of paediatric metabolic syndrome and type 2 diabetes mellitus. Diab Vasc Dis Res 4:285–296

    PubMed  Google Scholar 

  162. Haberland M, Montgomery RL, Olson EN (2009) The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10:32–42. doi:10.1038/nrg2485

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Milagro FI, Gómez-Abellán P, Campión J, Martínez JA, Ordovás JM, Garaulet M (2012) CLOCK, PER2 and BMAL1 DNA methylation: association with obesity and metabolic syndrome characteristics and monounsaturated fat intake. Chronobiol Int 29:1180–1194. doi:10.3109/07420528.2012.719967

    CAS  PubMed  Google Scholar 

  164. Copeland RA, Olhava EJ, Scott MP (2010) Targeting epigenetic enzymes for drug discovery. Curr Opin Chem Biol 14:505–510. doi:10.1016/j.cbpa.2010.06.174

    CAS  PubMed  Google Scholar 

  165. Chase K, Sharma RP (2013) Epigenetic developmental programs and adipogenesis: implications for psychotropic induced obesity. Epigenetics 8:1133–1140

    CAS  PubMed  Google Scholar 

  166. Soubry A, Schildkraut JM, Murtha A, Wang F, Huang Z, Bernal A, Kurtzberg J, Jirtle RL, Murphy SK, Hoyo C (2013) Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a newborn epigenetics study (NEST) cohort. BMC Med 11:29. doi:10.1186/1741-7015-11-29

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Vucetic Z, Carlin JL, Totoki K, Reyes TM (2012) Epigenetic dysregulation of the dopamine system in diet-induced obesity. J Neurochem 120:891–898. doi:10.1111/j.1471-4159.2012.07649.x

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Zhang Y, Kent JW 2nd, Lee A, Cerjak D, Ali O, Diasio R, Olivier M, Blangero J, Carless MA, Kissebah AH (2013) Fatty acid binding protein 3 (fabp3) is associated with insulin, lipids and cardiovascular phenotypes of the metabolic syndrome through epigenetic modifications in a Northern European family population. BMC Med Genomics 6:9. doi:10.1186/1755-8794-6-9

    PubMed  PubMed Central  Google Scholar 

  169. Ling C, Del Guerra S, Lupi R, Rönn T, Granhall C, Luthman H, Masiello P, Marchetti P, Groop L, Del Prato S (2008) Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion. Diabetologia 51:615–622. doi:10.1007/s00125-007-0916-5

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Yang BT, Dayeh TA, Volkov PA, Kirkpatrick CL, Malmgren S, Jing X, Renström E, Wollheim CB, Nitert MD, Ling C (2012) Increased DNA methylation and decreased expression of PDX-1 in pancreatic islets from patients with type 2 diabetes. Mol Endocrinol 26:1203–1212. doi:10.1210/me.2012-1004

    CAS  PubMed  Google Scholar 

  171. Kulkarni SS, Salehzadeh F, Fritz T, Zierath JR, Krook A, Osler ME (2012) Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus. Metabolism 61:175–185. doi:10.1016/j.metabol.2011.06.014

    CAS  PubMed  Google Scholar 

  172. Yang BT, Dayeh TA, Kirkpatrick CL, Taneera J, Kumar R, Groop L, Wollheim CB, Nitert MD, Ling C (2011) Insulin promoter DNA methylation correlates negatively with insulin gene expression and positively with HbA(1c) levels in human pancreatic islets. Diabetologia 54:360–367. doi:10.1007/s00125-010-1967-6

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Hall E, Dayeh T, Kirkpatrick CL, Wollheim CB, Dekker Nitert M, Ling C (2013) DNA methylation of the glucagon-like peptide 1 receptor (GLP1R) in human pancreatic islets. BMC Med Genet 14:76. doi:10.1186/1471-2350-14-76

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Ribel-Madsen R, Fraga MF, Jacobsen S, Bork-Jensen J, Lara E, Calvanese V, Fernandez AF, Friedrichsen M, Vind BF, Højlund K, Beck-Nielsen H, Esteller M, Vaag A, Poulsen P (2012) Genome-wide analysis of DNA methylation differences in muscle and fat from monozygotic twins discordant for type 2 diabetes. PLoS One 7:e51302. doi:10.1371/journal.pone.0051302

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Slomko H, Heo HJ, Einstein FH (2012) Minireview: epigenetics of obesity and diabetes in humans. Endocrinology 153:1025–1030. doi:10.1210/en.2011-1759

    CAS  PubMed  PubMed Central  Google Scholar 

  176. Yokomori N, Tawata M, Onaya T (1999) DNA demethylation during the differentiation of 3T3-L1 cells affects the expression of the mouse GLUT4 gene. Diabetes 48:685–690

    CAS  PubMed  Google Scholar 

  177. Fujiki K, Kano F, Shiota K, Murata M (2009) Expression of the peroxisome proliferator activated receptor gamma gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes. BMC Biol 7:38. doi:10.1186/1741-7007-7-38

    PubMed  PubMed Central  Google Scholar 

  178. Drummond EM, Gibney ER (2013) Epigenetic regulation in obesity. Curr Opin Clin Nutr Metab Care 16:392–397. doi:10.1097/MCO.0b013e3283620f45

    CAS  PubMed  Google Scholar 

  179. Pescador N, Pérez-Barba M, Ibarra JM, Corbatón A, Martínez-Larrad MT, Serrano-Ríos M (2013) Serum circulating microRNA profiling for identification of potential type 2 diabetes and obesity biomarkers. PLoS One 8:e77251. doi:10.1371/journal.pone.0077251

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Pan S, Yang X, Jia Y, Li R, Zhao R (2013) Microvesicle-shuttled miR-130b reduces fat deposition in recipient primary cultured porcine adipocytes by inhibiting PPAR-γ expression. J Cell Physiol. doi:10.1002/jcp.24486

    Google Scholar 

  181. Crépin D, Benomar Y, Riffault L, Amine H, Gertler A, Taouis M (2014) The over-expression of miR-200a in the hypothalamus of ob/ob mice is linked to leptin and insulin signaling impairment. Mol Cell Endocrinol 384:1–11. doi:10.1016/j.mce.2013.12.016

    PubMed  Google Scholar 

  182. Hulsmans M, De Keyzer D, Holvoet P (2011) Micro- RNAs regulating oxidative stress and inflammation in relation to obesity and atherosclerosis. FASEB J 25:2515–2527. doi:10.1096/fj.11-181149

    CAS  PubMed  Google Scholar 

  183. Ortega FJ, Moreno-Navarrete JM, Pardo G, Sabater M, Hummel M, Ferrer A, Rodriguez-Hermosa JI, Ruiz B, Ricart W, Peral B, Fernández-Real JM (2010) MiRNA expression profile of human subcutaneousnadipose and during adipocyte differentiation. PLoS One 5:e9022. doi:10.1371/journal.pone.0009022

    PubMed  PubMed Central  Google Scholar 

  184. Bastos Sales L, Kamstra JH, Cenijn PH, van Rijt LS, Hamers T, Legler J (2013) Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation. Toxicol In Vitro 27:1634–1643. doi:10.1016/j.tiv.2013.04.005

    CAS  PubMed  Google Scholar 

  185. Mirmira P, Evans-Molina C (2014) Bisphenol A, obesity, and type 2 diabetes mellitus: genuine concern or unnecessary preoccupation? Transl Res 164:13–21. doi:10.1016/j.trsl.2014.03.003

    CAS  PubMed  Google Scholar 

  186. van Esterik JC, Dollé ME, Lamoree MH, van Leeuwen SP, Hamers T, Legler J, van der Ven LT (2014) Programming of metabolic effects in C57BL/6JxFVB mice by exposure to bisphenol A during gestation and lactation. Toxicology 32:40–52. doi:10.1016/j.tox.2014.04.001

    Google Scholar 

  187. Janesick A, Blumberg B (2012) Obesogens, stem cells and the developmental programming of obesity. Int J Androl 35:437–448. doi:10.1111/j.1365-2605.2012.01247.x

    CAS  PubMed  PubMed Central  Google Scholar 

  188. Skinner MK, Manikkam M, Tracey R, Guerrero-Bosagna C, Haque M, Nilsson EE (2013) Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity. BMC Med 11:228. doi:10.1186/1741-7015-11-228

    PubMed  PubMed Central  Google Scholar 

  189. Scinicariello F, Buser MC (2014) Urinary polycyclic aromatic hydrocarbons and childhood obesity: NHANES (2001–2006). Environ Health Perspect 122:299–303. doi:10.1289/ehp.1307234

    PubMed  PubMed Central  Google Scholar 

  190. Slotkin TA (2011) Does early-life exposure to organophosphate insecticides lead to prediabetes and obesity? Reprod Toxicol 31:297–301

    CAS  PubMed  PubMed Central  Google Scholar 

  191. Lind L, Zethelius B, Salihovic S, van Bavel B, Lind PM (2014) Circulating levels of perfluoroalkyl substances and prevalent diabetes in the elderly. Diabetologia 57:473–479. doi:10.1007/s00125-013-3126-3

    CAS  PubMed  Google Scholar 

  192. Warner M, Mocarelli P, Brambilla P, Wesselink A, Samuels S, Signorini S, Eskenazi B (2013) Diabetes, metabolic syndrome, and obesity in relation to serum dioxin concentrations: the Seveso women’s health study. Environ Health Perspect 121:906–911. doi:10.1289/ehp.1206113

    PubMed  PubMed Central  Google Scholar 

  193. Buser MC, Murray HE, Scinicariello F (2014) Age and sex differences in childhood and adulthood obesity association with phthalates: analyses of NHANES 2007–2010. Int J Hyg Environ Health 217:687–694. doi:10.1016/j.ijheh.2014.02.005

    PubMed  Google Scholar 

  194. Hao CJ, Cheng XJ, Xia HF, Ma X (2012) The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice. Toxicol Appl Pharmacol 263:102–110

    CAS  PubMed  Google Scholar 

  195. Gai W, Schott-Ohly P, Schulte im Walde S, Gleichmann H (2004) Differential target molecules for toxicity induced by streptozotocin and alloxan in pancreatic islets of mice in vitro. Exp Clin Endocrinol Diabetes 112:29–37

    CAS  PubMed  Google Scholar 

  196. Wilson C (2012) Metabolism: iron metabolism, adiponectin and T2DM—The link with adipocyte insulin resistance. Nat Rev Endocrinol 8:696

    Google Scholar 

  197. Garrido-Sanchez L, Garcia-Fuentes E, Fernandez-Garcia D, Escote X, Alcaide J, Perez-Martinez P, Vendrell J, Tinahones FJ (2012) Zinc-alpha 2-glycoprotein gene expression in adipose tissue is related with insulin resistance and lipolytic genes in morbidly obese patients. PLoS One 7:e33264

    CAS  PubMed  PubMed Central  Google Scholar 

  198. Strakovsky RS, Lezmi S, Flaws JA, Schantz SL, Pan YX, Helferich WG (2014) Genistein exposure during the early postnatal period favors the development of obesity in female, but not male rats. Toxicol Sci 138:161–174

    CAS  PubMed  PubMed Central  Google Scholar 

  199. Gao Y-J, Holloway AC, Zeng ZH, Lim GE, Petrik JJ, Foster WG, Lee RM (2005) Prenatal exposure to nicotine causes postnatal obesity and altered perivascular adipose tissue function. Obes Res 13:687–692

    PubMed  Google Scholar 

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Authors and Affiliations

  1. European Cancer and Environment Research Institute (ECERI), Brussels, Belgium

    Ernesto Burgio

  2. ISDE International Society of Doctors for Environment Scientific Office, Arezzo, Italy

    Ernesto Burgio

  3. Department of Translational Research and New Technologies in Medicine and Surgery, Medical Genetics Laboratories, University of Pisa, Pisa, Italy

    Angela Lopomo & Lucia Migliore

  4. Doctoral School in Genetics, Oncology and Clinical Medicine, University of Siena, Siena, Italy

    Angela Lopomo

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Burgio, E., Lopomo, A. & Migliore, L. Obesity and diabetes: from genetics to epigenetics. Mol Biol Rep 42, 799–818 (2015). https://doi.org/10.1007/s11033-014-3751-z

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