Skip to main content
SpringerLink
Log in

Evidence for Epigenetic Changes as a Cause of Clinical Obesity

  • Chapter
  • First Online:
Obesity Before Birth

Part of the book series: Endocrine Updates ((ENDO,volume 30))

  • 1333 Accesses

Abstract

There is substantial evidence from epidemiology and from animal models that risk of obesity and its related conditions is modified by the quality of the early life environment, in particular, nutrition, behavior, and exposure to hormones. Such exposures represent signals which act through developmental plasticity to induce variation in the phenotype of the offspring. Induction of alternative phenotypes during development in response to environmental cues is consistent with a number of examples from nature in which, under appropriate conditions, the induced phenotype is adaptive. Recent studies in animal models and in humans show that induction of an altered phenotype during early life by social and nutritional stressors involves altered epigenetic regulation of specific non-imprinted genes by DNA methylation and histone modifications. Induced changes in DNA methylation involve alteration of a few specific CpG dinucleotides within the promoter region and are associated with changes in the mRNA expression and activity of DNA methyltransferases. There are some encouraging recent findings which show that for at least some early life exposures induction of an altered phenotype and epigenotype can be prevented or modified by nutritional interventions. Together these findings suggest the possibility of novel epigenetic biomarkers and therapeutic interventions to reduce the risk for obesity in later life.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Hossain P, Kawar B, El NM. Obesity and diabetes in the developing world–a growing challenge. N Engl J Med. 2007;356:213–5.

    Article  CAS  PubMed  Google Scholar 

  2. Andreasen CH, Andersen G. Gene-environment interactions and obesity–further aspects of genomewide association studies. Nutrition. 2009;25:998–1003.

    Article  CAS  PubMed  Google Scholar 

  3. Manolio TA. Cohort studies and the genetics of complex disease. Nat Genet. 2009;41:5–6.

    Article  CAS  PubMed  Google Scholar 

  4. Waddington CH. Canalization of development and the inheritance of acquired characters. Nature. 1942;150:563–5.

    Article  Google Scholar 

  5. Stockard CR. Developmental rate and structural expression: an experimental study of twins, double monsters and single deformities, and the interaction among embryonic organs during their origin and development. Am J Anatomy. 1921;28:115–277.

    Article  Google Scholar 

  6. Pener MP, Yerushalmi Y. The physiology of locust phase polymorphism: an update. J Insect Physiol. 1998;44:365–77.

    Article  CAS  PubMed  Google Scholar 

  7. Laforsch C, Tollrian R. Embryological aspects of inducible morphological defenses in Daphnia. J Morphol. 2004;262:701–7.

    Article  PubMed  Google Scholar 

  8. Lee TM, Zucker I. Vole Infant Development is influenced perinatally by maternal photoperiodic history. Am J Physiol. 1988;255:R831–8.

    CAS  PubMed  Google Scholar 

  9. Kucharski R, Maleszka J, Foret S, Maleszka R. Nutritional control of reproductive status in honeybees via DNA methylation. Science. 2008;319:1827–30.

    Article  CAS  PubMed  Google Scholar 

  10. Waddington CH. Canalization of development and genetic assimilation of acquired characters. Nature. 1959;183:1654–5.

    Article  CAS  PubMed  Google Scholar 

  11. Gluckman PD, Hanson MA. Living with the past: evolution, development, and patterns of disease. Science. 2004;305:1733–6.

    Article  CAS  PubMed  Google Scholar 

  12. Jones KL, Smith DW. Recognition of the fetal alcohol syndrome in early infancy. Lancet. 1973;302:999–1001.

    Article  CAS  PubMed  Google Scholar 

  13. McBride WG. Thalidomide embryopathy. Teratology. 1977;16:79–82.

    Article  CAS  PubMed  Google Scholar 

  14. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008;359:61–73.

    Article  CAS  PubMed  Google Scholar 

  15. Burdge GC, Lillycrop KA, Jackson AA. Nutrition in early life, and risk of cancer and metabolic disease: alternative endings in an epigenetic tale? Br J Nutr. 2009;101:619–30.

    Article  CAS  PubMed  Google Scholar 

  16. Barker DJ, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet. 1986;1:1077–81.

    Article  CAS  PubMed  Google Scholar 

  17. Godfrey KM, Barker DJ. Fetal programming and adult health. Public Health Nutr. 2001;4:611–24.

    Article  CAS  PubMed  Google Scholar 

  18. Curhan GC, Chertow GM, Willett WC, et al. Birth weight and adult hypertension and obesity in women. Circulation. 1996;94:1310–5.

    Article  CAS  PubMed  Google Scholar 

  19. McCance DR, Pettitt DJ, Hanson RL, Jacobsson LT, Knowler WC, Bennett PH. Birth weight and non-insulin dependent diabetes: thrifty genotype, thrifty phenotype, or surviving small baby genotype? BMJ. 1994;308:942–5.

    Article  CAS  PubMed  Google Scholar 

  20. Painter RC, Roseboom TJ, Bleker OP. Prenatal exposure to the Dutch famine and disease in later life: an overview. Reprod Toxicol. 2005;20:345–52.

    Article  CAS  PubMed  Google Scholar 

  21. Cleal JK, Poore KR, Boullin JP, et al. Mismatched pre- and postnatal nutrition leads to cardiovascular dysfunction and altered renal function in adulthood. Proc Natl Acad Sci USA. 2007;104:9529–33.

    Article  CAS  PubMed  Google Scholar 

  22. Silverman BL, Rizzo TA, Cho NH, Metzger BE. Long-term effects of the intrauterine environment. The Northwestern University Diabetes in Pregnancy Center. Diabetes Care. 1998;21 Suppl 2:B142–9.

    PubMed  Google Scholar 

  23. Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics. 2005;115:e290–6.

    Article  PubMed  Google Scholar 

  24. Dorner G, Plagemann A. Perinatal hyperinsulinism as possible predisposing factor for diabetes mellitus, obesity and enhanced cardiovascular risk in later life. Horm Metab Res. 1994;26:213–21.

    Article  CAS  PubMed  Google Scholar 

  25. Oken E, Taveras EM, Kleinman KP, Rich-Edwards JW, Gillman MW. Gestational weight gain and child adiposity at age 3 years. Am J Obstet Gynecol. 2007;196:322–8.

    Article  PubMed  Google Scholar 

  26. Villamor E, Cnattingius S. Interpregnancy weight change and risk of adverse pregnancy outcomes: a population-based study. Lancet. 2006;368:1164–70.

    Article  PubMed  Google Scholar 

  27. Kral JG, Biron S, Simard S, et al. Large maternal weight loss from obesity surgery prevents transmission of obesity to children who were followed for 2 to 18 years. Pediatrics. 2006;118:e1644–9.

    Article  PubMed  Google Scholar 

  28. Poissonnet CM, LaVelle M, Burdi AR. Growth and development of adipose tissue. J Pediatr. 1988;113:1–9.

    Article  CAS  PubMed  Google Scholar 

  29. Catalano PM, Kirwan JP. Maternal factors that determine neonatal size and body fat. Curr Diab Rep. 2001;1:71–7.

    Article  CAS  PubMed  Google Scholar 

  30. Rolland-Cachera MF, Deheeger M, Bellisle F, Sempe M, Guilloud-Bataille M, Patois E. Adiposity rebound in children: a simple indicator for predicting obesity. Am J Clin Nutr. 1984;39:129–35.

    CAS  PubMed  Google Scholar 

  31. Ong KK, Ahmed ML, Emmett PM, Preece MA, Dunger DB. Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. BMJ. 2000;320:967–71.

    Article  CAS  PubMed  Google Scholar 

  32. Ong KK. Size at birth, postnatal growth and risk of obesity. Horm Res. 2006;65 Suppl 3:65–9.

    Article  CAS  PubMed  Google Scholar 

  33. Singhal A, Lucas A. Early origins of cardiovascular disease: is there a unifying hypothesis? Lancet. 2004;363:1642–5.

    Article  PubMed  Google Scholar 

  34. Singhal A. Early nutrition and long-term cardiovascular health. Nutr Rev. 2006;64:S44–9.

    Article  PubMed  Google Scholar 

  35. Harder T, Bergmann R, Kallischnigg G, Plagemann A. Duration of breastfeeding and risk of overweight: a meta-analysis. Am J Epidemiol. 2005;162:397–403.

    Article  PubMed  Google Scholar 

  36. Owen CG, Martin RM, Whincup PH, vey-Smith G, Gillman MW, Cook DG. The effect of breastfeeding on mean body mass index throughout life: a quantitative review of published and unpublished observational evidence. Am J Clin Nutr. 2005;82:1298–307.

    CAS  PubMed  Google Scholar 

  37. Gluckman PD, Hanson MA. Changing times: the evolution of puberty. Mol Cell Endocrinol. 2006;254–255:26–31.

    Article  PubMed  CAS  Google Scholar 

  38. Langley SC, Jackson AA. Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets. Clin Sci (Lond). 1994;86:217–22.

    CAS  Google Scholar 

  39. Lucas A, Baker BA, Desai M, Hales CN. Nutrition in pregnant or lactating rats programs lipid metabolism in the offspring. Br J Nutr. 1996;76:605–12.

    Article  CAS  PubMed  Google Scholar 

  40. Bellinger L, Lilley C, Langley-Evans SC. Prenatal exposure to a maternal low-protein diet programmes a preference for high-fat foods in the young adult rat. Br J Nutr. 2004;92:513–20.

    Article  CAS  PubMed  Google Scholar 

  41. Bellinger L, Sculley DV, Langley-Evans SC. Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats. Int J Obes (Lond). 2006;30:729–38.

    Article  CAS  Google Scholar 

  42. Burdge GC, Lillycrop KA, Jackson AA, Gluckman PD, Hanson MA. The nature of the growth pattern and of the metabolic response to fasting in the rat are dependent upon the dietary protein and folic acid intakes of their pregnant dams and post-weaning fat consumption. Br J Nutr. 2008;99:540–9.

    Article  CAS  PubMed  Google Scholar 

  43. Torrens C, Brawley L, Anthony FW, et al. Folate supplementation during pregnancy improves offspring cardiovascular dysfunction induced by protein restriction. Hypertension. 2006;47:982–7.

    Article  CAS  PubMed  Google Scholar 

  44. Calder PC, Yaqoob P. The level of protein and type of fat in the diet of pregnant rats both affect lymphocyte function in the offspring. Nutr Res. 2000;20:995–1005.

    Article  CAS  Google Scholar 

  45. Langley-Evans SC, Sculley DV. Programming of hepatic antioxidant capacity and oxidative injury in the ageing rat. Mech Ageing Dev. 2005;126:804–12.

    Article  CAS  PubMed  Google Scholar 

  46. Burdge GC, Hanson MA, Slater-Jefferies JL, Lillycrop KA. Epigenetic regulation of transcription: a mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life? Br J Nutr. 2007;97:1036–46.

    Article  CAS  PubMed  Google Scholar 

  47. Bertram C, Trowern AR, Copin N, Jackson AA, Whorwood CB. The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology. 2001;142:2841–53.

    Article  CAS  PubMed  Google Scholar 

  48. Burns SP, Desai M, Cohen RD, et al. Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation. J Clin Invest. 1997;100:1768–74.

    Article  CAS  PubMed  Google Scholar 

  49. Maloney CA, Gosby AK, Phuyal JL, Denyer GS, Bryson JM, Caterson ID. Site-specific changes in the expression of fat-partitioning genes in weanling rats exposed to a low-protein diet in utero. Obes Res. 2003;11:461–8.

    Article  CAS  PubMed  Google Scholar 

  50. Burdge GC, Phillips ES, Dunn RL, Jackson AA, Lillycrop KA. Effect of reduced maternal protein consumption during pregnancy in the rat on plasma lipid concentrations and expression of peroxisomal proliferator–activated receptors in the liver and adipose tissue of the offspring. Nutr Res. 2004;24:639–46.

    Article  CAS  Google Scholar 

  51. Lillycrop KA, Phillips ES, Jackson AA, Hanson MA, Burdge GC. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr. 2005;135:1382–6.

    CAS  PubMed  Google Scholar 

  52. Woodall SM, Johnston BM, Breier BH, Gluckman PD. Chronic maternal undernutrition in the rat leads to delayed postnatal growth and elevated blood pressure of offspring. Pediatr Res. 1996;40:438–43.

    Article  CAS  PubMed  Google Scholar 

  53. Roseboom T, de RS, Painter R. The Dutch famine and its long-term consequences for adult health. Early Hum Dev. 2006;82:485–91.

    Article  PubMed  Google Scholar 

  54. Gluckman PD, Lillycrop KA, Vickers MH, et al. Metabolic plasticity during mammalian development is directionally dependent on early nutritional status. Proc Natl Acad Sci USA. 2007;104:12796–800.

    Article  CAS  PubMed  Google Scholar 

  55. Lillycrop KA, Rodford J, Garratt ES, et al. Maternal diet during pregnancy induces specific changes in the hepatic transcriptome of the adult male offspring. Br J Nutr. 2010; doi:10.1017/S0007114509993795.

    Google Scholar 

  56. Morris TJ, Vickers M, Gluckman P, Gilmour S, Affara N. Transcriptional profiling of rats subjected to gestational undernourishment: implications for the developmental variations in metabolic traits. PLoS One. 2009;4:e7271.

    Article  PubMed  CAS  Google Scholar 

  57. Goldberg AD, Allis CD, Bernstein E. Epigenetics: a landscape takes shape. Cell. 2007;128:635–8.

    Article  CAS  PubMed  Google Scholar 

  58. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16:6–21.

    Article  CAS  PubMed  Google Scholar 

  59. Razin A, Szyf M. DNA methylation patterns. Formation and function. Biochim Biophys Acta. 1984;782:331–42.

    Article  CAS  PubMed  Google Scholar 

  60. Bird AP. Functions for DNA methylation in vertebrates. Cold Spring Harb Symp Quant Biol. 1993;58:281–5.

    Article  CAS  PubMed  Google Scholar 

  61. Bird A, Macleod D. Reading the DNA methylation signal. Cold Spring Harb Symp Quant Biol. 2004;69:113–8.

    Article  CAS  PubMed  Google Scholar 

  62. Bird AP, Wolffe AP. Methylation-induced repression–belts, braces, and chromatin. Cell. 1999;99:451–4.

    Article  CAS  PubMed  Google Scholar 

  63. Fuks F, Hurd PJ, Wolf D, Nan X, Bird AP, Kouzarides T. The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem. 2003;278:4035–40.

    Article  CAS  PubMed  Google Scholar 

  64. Strahl BD, Ohba R, Cook RG, Allis CD. Methylation of histone H3 at lysine 4 is highly conserved and correlates with transcriptionally active nuclei in Tetrahymena. Proc Natl Acad Sci USA. 1999;96:14967–72.

    Article  CAS  PubMed  Google Scholar 

  65. Lachner M, O’Carroll D, Rea S, Mechtler K, Jenuwein T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature. 2001;410:116–20.

    Article  CAS  PubMed  Google Scholar 

  66. Zegerman P, Canas B, Pappin D, Kouzarides T. Histone H3 lysine 4 methylation disrupts binding of nucleosome remodeling and deacetylase (NuRD) repressor complex. J Biol Chem. 2002;277:11621–4.

    Article  CAS  PubMed  Google Scholar 

  67. Nakayama J, Rice JC, Strahl BD, Allis CD, Grewal SI. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science. 2001;292:110–3.

    Article  CAS  PubMed  Google Scholar 

  68. Fuks F, Burgers WA, Brehm A, Hughes-Davies L, Kouzarides T. DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat Genet. 2000;24:88–91.

    Article  CAS  PubMed  Google Scholar 

  69. Rountree MR, Bachman KE, Baylin SB. DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nat Genet. 2000;25:269–77.

    Article  CAS  PubMed  Google Scholar 

  70. Vire E, Brenner C, Deplus R, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006;439:871–4.

    Article  CAS  PubMed  Google Scholar 

  71. Li E, Beard C, Jaenisch R. Role for DNA methylation in genomic imprinting. Nature. 1993;366:362–5.

    Article  CAS  PubMed  Google Scholar 

  72. Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development. Science. 2001;293:1089–93.

    Article  CAS  PubMed  Google Scholar 

  73. Bird A. Molecular biology. Methylation talk between histones and DNA. Science. 2001;294:2113–5.

    Article  CAS  PubMed  Google Scholar 

  74. Gidekel S, Bergman Y. A unique developmental pattern of Oct-3/4 DNA methylation is controlled by a cis-demodification element. J Biol Chem. 2002;277:34521–30.

    Article  CAS  PubMed  Google Scholar 

  75. Hershko AY, Kafri T, Fainsod A, Razin A. Methylation of HoxA5 and HoxB5 and its relevance to expression during mouse development. Gene. 2003;302:65–72.

    Article  CAS  PubMed  Google Scholar 

  76. Benvenisty N, Szyf M, Mencher D, Razin A, Reshef L. Tissue-specific hypomethylation and expression of rat phosphoenolpyruvate carboxykinase gene induced by in vivo treatment of fetuses and neonates with 5-azacytidine. Biochemistry. 1985;24:5015–9.

    Article  CAS  PubMed  Google Scholar 

  77. Grainger RM, Hazard-Leonards RM, Samaha F, Hougan LM, Lesk MR, Thomsen GH. Is hypomethylation linked to activation of delta-crystallin genes during lens development? Nature. 1983;306:88–91.

    Article  CAS  PubMed  Google Scholar 

  78. Dolinoy DC, Das R, Weidman JR, Jirtle RL. Metastable epialleles, imprinting, and the fetal origins of adult diseases. Pediatr Res. 2007;61:30R–7R.

    Article  PubMed  Google Scholar 

  79. Heijmans BT, Tobi EW, Stein AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA. 2008;105:17046–9.

    Article  CAS  PubMed  Google Scholar 

  80. Tobi EW, Lumey LH, Talens RP, et al. DNA Methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009;18:4046–53.

    Article  CAS  PubMed  Google Scholar 

  81. Bouchard L, Rabasa-Lhoret R, Faraj M, et al. Differential epigenomic and transcriptomic responses in subcutaneous adipose tissue between low and high responders to caloric restriction. Am J Clin Nutr. 2009;91:309–20.

    Article  PubMed  CAS  Google Scholar 

  82. Einstein F, Thompson RF, Bhagat TD, et al. Cytosine methylation dysregulation in neonates following intrauterine growth restriction. PLoS One. 2010;5:e8887.

    Article  PubMed  CAS  Google Scholar 

  83. Yamagata K, Furuta H, Oda N, et al. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1. Nature. 1996;384:458–60.

    Article  CAS  PubMed  Google Scholar 

  84. Burdge GC, Slater-Jefferies J, Torrens C, Phillips ES, Hanson MA, Lillycrop KA. 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. 2007;97:435–9.

    Article  CAS  PubMed  Google Scholar 

  85. Lillycrop KA, Slater-Jefferies JL, Hanson MA, Godfrey KM, Jackson AA, Burdge GC. Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications. Br J Nutr. 2007;97:1064–73.

    Article  CAS  PubMed  Google Scholar 

  86. Lillycrop KA, Phillips ES, Torrens C, Hanson MA, Jackson AA, Burdge GC. Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPARalpha promoter of the offspring. Br J Nutr. 2008;100:278–82.

    Article  CAS  PubMed  Google Scholar 

  87. Bogdarina I, Welham S, King PJ, Burns SP, Clark AJ. Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. Circ Res. 2007;100:520–6.

    Article  CAS  PubMed  Google Scholar 

  88. Plagemann A, Harder T, Brunn M, et al. Hypothalamic proopiomelanocortin promoter methylation becomes altered by early overfeeding: an epigenetic model of obesity and the metabolic syndrome. J Physiol. 2009;587:4963–76.

    Article  CAS  PubMed  Google Scholar 

  89. Milagro FI, Campion J, Garcia-Diaz DF, Goyenechea E, Paternain L, Martinez JA. High fat diet-induced obesity modifies the methylation pattern of leptin promoter in rats. J Physiol Biochem. 2009;65:1–9.

    Article  CAS  PubMed  Google Scholar 

  90. Bhattacharya SK, Ramchandani S, Cervoni N, Szyf M. A mammalian protein with specific demethylase activity for mCpG DNA. Nature. 1999;397:579–83.

    Article  CAS  PubMed  Google Scholar 

  91. Zhu B, Zheng Y, Angliker H, et al. 5-Methylcytosine DNA glycosylase activity is also present in the human MBD4 (G/T mismatch glycosylase) and in a related avian sequence. Nucleic Acids Res. 2000;28:4157–65.

    Article  CAS  PubMed  Google Scholar 

  92. Barreto G, Schafer A, Marhold J, et al. Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature. 2007;445:671–5.

    Article  CAS  PubMed  Google Scholar 

  93. Jost JP. Nuclear extracts of chicken embryos promote an active demethylation of DNA by excision repair of 5-methyldeoxycytidine. Proc Natl Acad Sci USA. 1993;90:4684–8.

    Article  CAS  PubMed  Google Scholar 

  94. Lucarelli M, Fuso A, Strom R, Scarpa S. The dynamics of myogenin site-specific demethylation is strongly correlated with its expression and with muscle differentiation. J Biol Chem. 2001;276:7500–6.

    Article  CAS  PubMed  Google Scholar 

  95. Bruniquel D, Schwartz RH. Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nat Immunol. 2003;4:235–40.

    Article  CAS  PubMed  Google Scholar 

  96. Kersh EN. Impaired memory CD8 T cell development in the absence of methyl-CpG-binding domain protein 2. J Immunol. 2006;177:3821–6.

    CAS  PubMed  Google Scholar 

  97. Szyf M. The dynamic epigenome and its implications in toxicology. Toxicol Sci. 2007;100:7–23.

    Article  CAS  PubMed  Google Scholar 

  98. Szyf M. Epigenetics, DNA methylation, and chromatin modifying drugs. Annu Rev Pharmacol Toxicol. 2008;49:243–63.

    Article  CAS  Google Scholar 

  99. Jackson-Grusby L, Beard C, Possemato R, et al. Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nat Genet. 2001;27:31–9.

    Article  CAS  PubMed  Google Scholar 

  100. Chiang EP, Wang YC, Chen WW, Tang FY. Effects of insulin and glucose on cellular metabolic fluxes in homocysteine transsulfuration, remethylation, S-adenosylmethionine synthesis, and global deoxyribonucleic acid methylation. J Clin Endocrinol Metab. 2009;94:1017–25.

    Article  CAS  PubMed  Google Scholar 

  101. Waterland RA, Travisano M, Tahiliani KG, Rached MT, Mirza S. Methyl donor supplementation prevents transgenerational amplification of obesity. Int J Obes (Lond). 2008;32:1373–9.

    Article  CAS  Google Scholar 

  102. Burdge GC, Lillycrop KA, Phillips ES, Slater-Jefferies JL, Jackson AA, Hanson MA. Folic acid supplementation during the juvenile-pubertal period in rats modifies the phenotype and epigenotype induced by prenatal nutrition. J Nutr. 2009;139:1054–60.

    Article  CAS  PubMed  Google Scholar 

  103. Vickers MH, Gluckman PD, Coveny AH, et al. Neonatal leptin treatment reverses developmental programming. Endocrinology. 2005;146:4211–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Human Nutrition, University of Southampton School of Medicine, Southampton, SO16 6YD, UK

    Graham C. Burdge

  2. School of Biological Sciences, University of Southampton, Southampton, SO16 7PX, UK

    Karen A. Lillycrop

Authors
  1. Graham C. Burdge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karen A. Lillycrop
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Graham C. Burdge .

Editor information

Editors and Affiliations

  1. Director, Weight Assessment for Teen and, Division of Endocrinology, University of California, San Francisco, San Francisco, 94143, USA

    Robert H Lustig

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Burdge, G.C., Lillycrop, K.A. (2011). Evidence for Epigenetic Changes as a Cause of Clinical Obesity. In: Lustig, R. (eds) Obesity Before Birth. Endocrine Updates, vol 30. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7034-3_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-7034-3_7

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-7033-6

  • Online ISBN: 978-1-4419-7034-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation