Epigenetic Events Associated with Obesity and Diabetes

  • Ernesto Burgio
  • Lucia Migliore


Obesity is becoming a major public health concern. During the last years, genetic and epigenetic factors have been supposed to contribute to increase (or decrease) the susceptibility to gain weight and to develop obesity-related comorbidities. Metabolic syndrome, defined by a combination of disturbed glucose and insulin metabolism, central obesity, dyslipidemia, and hypertension, is considered to be a risk factor for type 2 diabetes and cardiovascular disease. The role of genetic factors involved in the etiology of human obesity is beyond question. Moreover there is evidence that the current epidemic of obesity and diabetes is environmentally driven. Studies during the past decade have indicated that normal metabolic regulation during adulthood not only requires a good matching of energy intake with energy expenditure, but also is influenced by fetal and postnatal environments. Epidemiological studies and experimental models show that maternal nutritional constraint during pregnancy alters the metabolic phenotype of the offspring and that this can be passed to subsequent generations. Recent researches in a number of laboratories all over the world suggest the continuous increase in the environment and food chains of “obesogens,” above all of endocrine disruptors, i.e., chemicals that interfere with many homeostatic mechanisms, altering the regulation of energy balance, promoting fat accumulation, adipogenesis, and weight gain. Finally epigenetic marks could be useful to personalize nutrition, to early detect those individuals with more risk to develop metabolic disorders or to better respond to a treatment.


Epigenetics Obesity Diabetes Metabolic syndrome Obesogens 


  1. Ahima RS (2006) Adipose tissue as an endocrine organ. Obesity (Silver Spring) 14:242S–249SGoogle Scholar
  2. Anderson EJ, Lustig ME, Boyle KE, Woodlief TL, Kane DA, Lin CT, Price JW 3rd, Kang L, Rabinovitch PS, Szeto HH, Houmard JA, Cortright RN, Wasserman DH, Neufer PD (2009) Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest 119:573–581PubMedCentralPubMedGoogle Scholar
  3. Antuna-Puente B, Feve B, Fellahi S, Bastard JP (2008) Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab 34:2–11PubMedGoogle Scholar
  4. Arner E, Westermark PO, Spalding KL, Britton T, Rydén M, Frisén J, Bernard S, Arner P (2010) Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes 59:105–109PubMedCentralPubMedGoogle Scholar
  5. 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 12:641–647PubMedGoogle Scholar
  6. 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 104:979–984PubMedCentralPubMedGoogle Scholar
  7. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 101:15718–15723PubMedCentralPubMedGoogle Scholar
  8. 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 5:563–564PubMedCentralPubMedGoogle Scholar
  9. Bell AC, Ge K, Popkin BM (2001) Weight gain and its predictors in Chinese adults. Int J Obes Relat Metab Disord 25:1079–1086PubMedGoogle Scholar
  10. 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–S32PubMedGoogle Scholar
  11. Bouret SG (2009) Early life origins of obesity: role of hypothalamic programming. J Pediatr Gastroenterol Nutr 48:S31–S38PubMedGoogle Scholar
  12. Bramswig NC, Kaestner KH (2012) Epigenetics and diabetes treatment: an unrealized promise? Trends Endocrinol Metab 23:286–291PubMedCentralPubMedGoogle Scholar
  13. Bruce KD, Cagampang FR, Argenton M, Zhang J, Ethirajan PL, Burdge GC, Bateman AC, Clough GF, Poston L, Hanson MA, Mcconnell JM, Byrne CD (2009) Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression. Hepatology 50:1796–1808PubMedGoogle Scholar
  14. Burdge GC, Slater-Jefferies J, Torrens C, Phillips ES, Hanson MA, Lillycrop KA (2007) Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. Br J Nutr 97:435–439PubMedCentralPubMedGoogle Scholar
  15. Choquet H, Meyre D (2011) Molecular basis of obesity: current status and future prospects. Curr Genomics 12:154–168PubMedCentralPubMedGoogle Scholar
  16. 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 U S A 108:4586–4591PubMedCentralPubMedGoogle Scholar
  17. Collins S (2005) Overview of clinical perspectives and mechanisms of obesity. Birth Defects Res A Clin Mol Teratol 73:470–471PubMedGoogle Scholar
  18. Copeland RA, Olhava EJ, Scott MP (2010) Targeting epigenetic enzymes for drug discovery. Curr Opin Chem Biol 14:505–510PubMedGoogle Scholar
  19. Cordero P, Campion J, Milagro FI, Goyenechea E, Steemburgo T, Javierre BM, Martinez JA (2011) Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet. J Physiol Biochem 67:463–470PubMedGoogle Scholar
  20. D’Angelo CS, Koiffmann CP (2012) Copy number variants in obesity-related syndromes: review and perspectives on novel molecular approaches. J Obes 2012:845480PubMedCentralPubMedGoogle Scholar
  21. Das UN (2001) Is obesity an inflammatory condition? Nutrition 17:953–966PubMedGoogle Scholar
  22. De Heredia FP, Gómez-Martínez S, Marcos A (2012) Obesity, inflammation and the immune system. Proc Nutr Soc 71:332–338PubMedGoogle Scholar
  23. Decherf S, Demeneix BA (2011) The obesogen hypothesis: a shift of focus from the periphery to the hypothalamus. J Toxicol Environ Health B Crit Rev 14:423–448PubMedGoogle Scholar
  24. Dethlefsen L, Mcfall-Ngai M, Relman DA (2007) An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature 449:811–818PubMedGoogle Scholar
  25. Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC (2009) Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 30:293–342PubMedCentralPubMedGoogle Scholar
  26. 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 83:460–469PubMedGoogle Scholar
  27. Dietz WH (1998) Health consequences of obesity in youth: childhood predictors of adult disease. Pediatrics 101:518–525PubMedGoogle Scholar
  28. Dietz WH, Gortmaker SL (2001) Preventing obesity in children and adolescents. Annu Rev Public Health 22:337–353PubMedGoogle Scholar
  29. Dolinoy DC (2008) The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr Rev 66:S7–S11PubMedCentralPubMedGoogle Scholar
  30. 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 U S A 107:11971–11975PubMedCentralPubMedGoogle Scholar
  31. Drong AW, Lindgren CM, McCarthy MI (2012) The genetic and epigenetic basis of type 2 diabetes and obesity. Clin Pharmacol Ther 92:707–715PubMedGoogle Scholar
  32. Fain JN (2010) Release of inflammatory mediators by human adipose tissue is enhanced in obesity and primarily by the nonfat cells: a review. Mediators Inflamm 2010:513948PubMedCentralPubMedGoogle Scholar
  33. Feinberg AP, Irizarry RA, Fradin D, Aryee MJ, Murakami P, Aspelund T, Eiriksdottir G, Harris TB, Launer L, Gudnason V, Fallin MD (2010) Personalized epigenomic signatures that are stable over time and covary with body mass index. Sci Transl Med 2:49ra67PubMedCentralPubMedGoogle Scholar
  34. Fleisch AF, Wright RO, Baccarelli AA (2012) Environmental epigenetics: a role in endocrine disease? J Mol Endocrinol 49:R61–R67PubMedCentralPubMedGoogle Scholar
  35. Freudenberg N (2011) The social science of obesity. Lancet 37:760Google Scholar
  36. Galili O, Versari D, Sattler KJ, Olson ML, Mannheim D, McConnell JP, Chade AR, Lerman LO, Lerman A (2007) Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress. Am J Physiol Heart Circ Physiol 292:H904–H911PubMedGoogle Scholar
  37. 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 32:2281–2287PubMedCentralPubMedGoogle Scholar
  38. Godfrey KM, Sheppard A, Gluckman PD, Lillycrop K, 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 60:1528–1534PubMedCentralPubMedGoogle Scholar
  39. Goran MI, Ball GDC, Cruz ML (2003) Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. J Clin Endocrinol Metab 88:1417–1427PubMedGoogle Scholar
  40. Greiner T, Bäckhed F (2011) Effects of the gut microbiota on obesity and glucose homeostasis. Trends Endocrinol Metab 22:117–123PubMedGoogle Scholar
  41. Grün F, Blumberg B (2006) Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology 147:S50–S55PubMedGoogle Scholar
  42. Grün F, Blumberg B (2007) Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis. Rev Endocr Metab Disord 8:161–171PubMedGoogle Scholar
  43. Grün F, Blumberg B (2009a) Minireview: the case for obesogens. Mol Endocrinol 23:1127–1134PubMedCentralPubMedGoogle Scholar
  44. Grün F, Blumberg B (2009b) Endocrine disrupters as obesogens. Mol Cell Endocrinol 304:19–29PubMedCentralPubMedGoogle Scholar
  45. Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, Slagboom PE, Lumey LH (2008) Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A 105:17046–17049PubMedCentralPubMedGoogle Scholar
  46. 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 98:467–475PubMedGoogle Scholar
  47. Hill JO, Peters JC (1998) Environmental contributions to the obesity epidemic. Science 280:1371–1374PubMedGoogle Scholar
  48. Hill JO, Wyatt HR, Reed GW, Peters JC (2003) Obesity and the environment: where do we go from here? Science 299:853–855PubMedGoogle Scholar
  49. Hirosumi J, Tuncman G, Chang L, Görgün CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333–336PubMedGoogle Scholar
  50. Hu FB (2011) Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes Care 34:1249–1257PubMedCentralPubMedGoogle Scholar
  51. Irigaray P, Newby JA, Lacomme S, Belpomme D (2007) Overweight/obesity and cancer genesis: more than a biological link. Biomed Pharmacother 61:665–678PubMedGoogle Scholar
  52. Janesick A, Blumberg B (2011) Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity. Birth Defects Res C Embryo Today 93:34–50PubMedGoogle Scholar
  53. 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 24:526–539PubMedCentralPubMedGoogle Scholar
  54. Klöting N, Fasshauer M, Dietrich A, Kovacs P, Schön MR, Kern M, Stumvoll M, Blüher M (2010) Insulin-sensitive obesity. Am J Physiol Endocrinol Metab 299:E506–E515PubMedGoogle Scholar
  55. Köbberling J, Tillil H (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, LondonGoogle Scholar
  56. Lafontan M, Berlan M (2003) Do regional differences in adipocyte biology provide new pathophysiological insights? Trends Pharmacol Sci 24:276–283PubMedGoogle Scholar
  57. Laudes M (2011) Role of WNT signalling in the determination of human mesenchymal stem cells into preadipocytes. J Mol Endocrinol 46:R65–R72PubMedGoogle Scholar
  58. Levin BE (2006) Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis. Philos Trans R Soc Lond B Biol Sci 361:1107–1121PubMedCentralPubMedGoogle Scholar
  59. Levin BE (2009) Synergy of nature and nurture in the development of childhood obesity. Int J Obes (Lond) 33:S53–S56Google Scholar
  60. Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444:1022–1023PubMedGoogle Scholar
  61. Libman IM, Pietropaolo M, Arslanian SA, Laporte RE, Becker DL (2003) Changing prevalence of overweight children and adolescents at onset of insulin-treated diabetes. Diabetes Care 26:2871–2875PubMedGoogle Scholar
  62. Lillycrop KA (2011) Effect of maternal diet on the epigenome: implications for human metabolic disease. Proc Nutr Soc 70:64–72PubMedGoogle Scholar
  63. Lobstein T, Bauer L, Uauy R (2004) Obesity in children and young people: a crisis in public health. Obes Rev 5:4–104PubMedGoogle Scholar
  64. Lopez KN, Knudson JD (2012) Obesity: from the agricultural revolution to the contemporary pediatric epidemic. Congenit Heart Dis 7:189–199PubMedGoogle Scholar
  65. 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(1):e55387PubMedCentralPubMedGoogle Scholar
  66. 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(2):276–283PubMedGoogle Scholar
  67. Mcallister EJ, Dhurandhar NV, Keith SW, Aronne LJ, Barger J, Baskin M, Benca RM, Biggio J, Boggiano MM, Eisenmann JC, Elobeid M, Fontaine KR, Gluckman P, Hanlon EC, Katzmarzyk P, Pietrobelli A, Redden DT, Ruden DM, Wang C, Waterland RA, Wright SM, Allison DB (2009) Ten putative contributors to the obesity epidemic. Crit Rev Food Sci Nutr 49:868–913PubMedCentralPubMedGoogle Scholar
  68. Milagro FI, Mansego ML, De Miguel C, Martínez JA (2013) Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives. Mol Aspects Med 34(4):782–812PubMedGoogle Scholar
  69. 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 289:76–79PubMedGoogle Scholar
  70. Musso G, Gambino R, Cassader M (2010) Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care 33:2277–2284PubMedCentralPubMedGoogle Scholar
  71. Neel BA, Sargis RM (2011) The paradox of progress: environmental disruption of metabolism and the diabetes epidemic. Diabetes 60:1838–1848PubMedCentralPubMedGoogle Scholar
  72. Newbold RR, Padilla-Banks E, Jefferson WN (2009) Environmental estrogens and obesity. Mol Cell Endocrinol 304:84–89PubMedCentralPubMedGoogle Scholar
  73. Newbold RR, Padilla-Banks E, Jefferson WN, Heindel JJ (2008) Effects of endocrine disruptors on obesity. Int J Androl 31:201–208PubMedGoogle Scholar
  74. Palmer C, Bik EM, Digiulio DB, Relman DA, Brown PO (2007) Development of the human infant intestinal microbiota. PLoS Biol 5:e177PubMedCentralPubMedGoogle Scholar
  75. Permutt MA, Wasson J, Cox N (2005) Genetic epidemiology of diabetes. J Clin Invest 115:1431–1439PubMedCentralPubMedGoogle Scholar
  76. Plagemann A (2008) A matter of insulin: developmental programming of body weight regulation. J Matern Fetal Neonatal Med 21:143–148PubMedGoogle Scholar
  77. Plagemann A, Harder T, Brunn M, Harder A, Roepke K, Wittrock-Staar M, Ziska T, Schellong K, Rodekamp E, Melchior K, Dudenhausen JW (2009) Hypothalamic proopiomelanocortin promoter methylation becomes altered by early overfeeding: an epigenetic model of obesity and the metabolic syndrome. J Physiol 587:4963–4976PubMedCentralPubMedGoogle Scholar
  78. 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 42:139–145PubMedGoogle Scholar
  79. Power C, Jefferis BJ (2002) Fetal environment and subsequent obesity: a study of maternal smoking. Int J Epidemiol 31:413–419PubMedGoogle Scholar
  80. Prior LJ, Armitage JA (2009) Neonatal overfeeding leads to developmental programming of adult obesity: you are what you ate. J Physiol 587:2419PubMedCentralPubMedGoogle Scholar
  81. 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 16:316–334PubMedGoogle Scholar
  82. Rubenstein AH (2005) Obesity: a modern epidemic. Trans Am Clin Climatol Assoc 116:103–113PubMedCentralPubMedGoogle Scholar
  83. Salsberry PJ, Reagan PB (2005) Dynamics of early childhood overweight. Pediatrics 116:1329–1338PubMedCentralPubMedGoogle Scholar
  84. Sapienza C, Lee J, Powell J, Erinle O, Yafai F, Reichert J, Siraj ES, Madaio M (2011) DNA methylation profiling identifies epigenetic differences between diabetes patients with ESRD and diabetes patients without nephropathy. Epigenetics 6:20–28PubMedGoogle Scholar
  85. 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 11:48PubMedCentralPubMedGoogle Scholar
  86. Schwimmer JB, Burwinkle TM, Varni JW (2003) Health-related quality of life severely obese children and adolescents. JAMA 289:1813–1819PubMedGoogle Scholar
  87. Sinha R, Fisch G, Teague B, Tamborlane WV, Banyas B, Allen K, Savoye M, Rieger V, Taksali S, Barbetta G, Sherwin RS, Caprio S (2002) Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 346:802–810PubMedGoogle Scholar
  88. 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 117:1549–1555PubMedCentralPubMedGoogle Scholar
  89. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Näslund E, Britton T, Concha H, Hassan M, Rydén M, Frisén J, Arner P (2008) Dynamics of fat cell turnover in humans. Nature 453:783–787PubMedGoogle Scholar
  90. Speakman JR, O’Rahilly S (2012) Fat: an evolving issue. Dis Model Mech 5:569–573PubMedCentralPubMedGoogle Scholar
  91. St-Onge MP, Keller KL, Heymsfield SB (2003) Changes in childhood food consumption patterns: a cause for concern in light of increasing body weights. Am J Clin Nutr 78:1068–1073PubMedGoogle Scholar
  92. Stubbs CO, Lee AJ (2004) The obesity epidemic: both energy intake and physical activity contribute. Med J Aust 181:489–491PubMedGoogle Scholar
  93. Stunkard AJ, Foch TT, Hrubec Z (1986a) A twin study of human obesity. JAMA 256:51–54PubMedGoogle Scholar
  94. Stunkard AJ, Sørensen TI, Hanis C, Teasdale TW, Chakraborty R, Schull WJ, Schulsinger F (1986b) An adoption study of human obesity. N Engl J Med 314:193–198PubMedGoogle Scholar
  95. Swinburn B, Egger G, Raza F (1999) Dissecting obesogenic environments: the development and application of a framework foridentifying and prioritizing environmental interventions for obesity. Prev Med 29:563–570PubMedGoogle Scholar
  96. Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD, Slagboom PE, Heijmans BT (2009) DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet 18:4046–4053PubMedCentralPubMedGoogle Scholar
  97. Toperoff G, Aran D, Kark JD, Rosenberg M, Dubnikov T, Nissan B, Wainstein J, Friedlander Y, Levy-Lahad E, Glaser B, Hellman A (2009) Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood. Hum Mol Genet 21:371–383Google Scholar
  98. 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 36:104–116PubMedCentralPubMedGoogle Scholar
  99. Tsai F, Coyle WJ (2009) The microbiome and obesity: is obesity linked to our gut flora? Curr Gastroenterol Rep 11:307–313PubMedGoogle Scholar
  100. 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 33:378–455PubMedCentralPubMedGoogle Scholar
  101. Vimaleswaran KS, Loos RJ (2010) Progress in the genetics of common obesity and type 2 diabetes. Expert Rev Mol Med 12:e7PubMedGoogle Scholar
  102. Wang G, Dietz WH (2002) Economic burden of obesity in youths aged 6 to 17 years: 1979–1999. Pediatrics 109:E81-1PubMedGoogle Scholar
  103. Waterland RA, Jirtle RL (2003) Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23:5293–5300PubMedCentralPubMedGoogle Scholar
  104. Wells JC (2012) The evolution of human adiposity and obesity: where did it all go wrong? Dis Model Mech 5:595–607PubMedCentralPubMedGoogle Scholar
  105. Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH (1997) Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med 337:869–873PubMedGoogle Scholar
  106. Whitman WB, Coleman DC, Wiebe WJ (1998) Prokaryotes: the unseen majority. Proc Natl Acad Sci U S A 95:6578–6583PubMedCentralPubMedGoogle Scholar
  107. Widschwendter M, Apostolidou S, Raum E, Rothenbacher D, Fiegl H, Menon U, Stegmaier C, Jacobs IJ, Brenner H (2008) Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. PLoS One 3(7):e2656PubMedCentralPubMedGoogle Scholar
  108. Xu J, Gordon JI (2003) Inaugural article: honor thy symbionts. Proc Natl Acad Sci U S A 100:10452–10459PubMedCentralPubMedGoogle Scholar
  109. 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 (2010) China National Diabetes and Metabolic Disorders Study Group. Prevalence of diabetes among men and women in China. N Engl J Med 362:1090–1110PubMedGoogle Scholar
  110. Zhang J, Zhang F, Didelot X, Bruce KD, Cagampang FR, Vatish M, Hanson M, Lehnert H, Ceriello A, Byrne CD (2009) Maternal high fat diet during pregnancy and lactation alters hepatic expression of insulin like growth factor-2 and key microRNAs in the adult offspring. BMC Genomics 10:478PubMedCentralPubMedGoogle Scholar
  111. 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 372:425–432PubMedGoogle Scholar
  112. Zhao J, Goldberg J, Vaccarino V (2013) Promoter methylation of serotonin transporter gene is associated with obesity measures: a monozygotic twin study. Int J Obes (Lond) 37(1):140–145Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.European Cancer and Environment Research Institute (ECERI)BruxellesBelgium
  2. 2.ISDE International Society of Doctors for Environment Scientific OfficeArezzoItaly
  3. 3.Department of Translational Research and New Technologies in Medicine and Surgery, Division of Medical GeneticsUniversity of PisaPisaItaly

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