Journal of Inherited Metabolic Disease

, Volume 29, Issue 2–3, pp 359–365 | Cite as

Impact of diets and nutrients/drugs on early epigenetic programming

  • Claudine JunienEmail author


Specific, often unbalanced diets are used to circumvent the metabolic defects of patients with monogenic inborn errors of metabolism. Human epidemiological studies and appropriately designed dietary interventions in animal models have provided considerable evidence to suggest that nutritional imbalance and metabolic disturbances, during critical time windows of developmental programming, may have a persistent effect on the health of the child and later in adulthood. Thus patients with monogenic inborn errors of metabolism may also suffer additional types of alterations due to the lack or excess of key nutrients. Interactions of nutrients with the epigenetic machinery lead to epigenetic changes associated with chromatin remodelling and regulation of gene expression that underlie the developmental programming of pathological consequences in adulthood. Today, with the explosion of new technologies, we can explore on a large scale the effects of nutrients on the level of expression of thousands of expressed genes (nutritional genomics and epigenomics), the corresponding protein products and their posttranslationally modified derivatives (proteomics), and the host of metabolites (metabolomics) generated from endogenous metabolic processes or exogenous dietary nutrients and can establish the relationship between these biological entities and diet, health or disease. The combination of these various lines of research on epigenetic programming processes should highlight new strategies for the prevention and treatment of inborn errors of metabolism.


Glucocorticoid Receptor Epigenetic Inheritance Epigenetic Programming Endogenous Metabolic Process Unbalanced Diet 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308: 1466–1469.PubMedCrossRefGoogle Scholar
  2. Armitage JA, Khan IY, Taylor PD, Nathanielsz PW, Poston L (2004) Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J Physiol 561(Pt 2): 355–377.PubMedCrossRefGoogle Scholar
  3. Barker DJ, Clark PM (1997) Fetal undernutrition and disease in later life. Rev Reprod 2(2): 105–112.PubMedCrossRefGoogle Scholar
  4. Boloker J, Gertz SJ, Simmons RA (2002) Gestational diabetes leads to the development of diabetes in adulthood in the rat. Diabetes 51(5): 1499–1506.PubMedGoogle Scholar
  5. Brown R, Strathdee G (2002) Epigenomics and epigenetic therapy of cancer. Trends Mol Med 8(4 Supplement): S43–48.PubMedCrossRefGoogle Scholar
  6. Dabelea D, Hanson RL, Lindsay RS, et al (2000) Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes 49(12): 2208–2211.PubMedGoogle Scholar
  7. Eckel RH, Grundy SM, Zimmet PZ (2005) The metabolic syndrome. Lancet 365(9468): 1415–1428.PubMedCrossRefGoogle Scholar
  8. Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429(6990): 457–463.PubMedCrossRefGoogle Scholar
  9. Gallou-Kabani C, Junien C (2005) Nutritional epigenomics of metabolic syndrome. Diabetes 54: 1899–1906.PubMedGoogle Scholar
  10. Han J, Xu J, Epstein PN, Liu YQ (2005) Long-term effect of maternal obesity on pancreatic beta cells of offspring: reduced beta cell adaptation to high glucose and high-fat diet challenges in adult female mouse offspring. Diabetologia 48(9): 1810–1818.PubMedCrossRefGoogle Scholar
  11. International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921.Google Scholar
  12. Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nature Genetics 33(Supplement): 245–254.PubMedCrossRefGoogle Scholar
  13. Kelly TL, Trasler JM (2004) Reproductive epigenetics. Clin Genet 65(4): 247–260.PubMedCrossRefGoogle Scholar
  14. Khan IY, Dekou V, Hanson M, Poston L, Taylor P (2004) Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring. Circulation 110: 1097–1102.PubMedCrossRefGoogle Scholar
  15. Khan IY, Dekou V, Douglas G, Jensen R, Hanson MA, Poston L, Taylor PD (2005) A high-fat diet during rat pregnancy or suckling induces cardiovascular dysfunction in adult offspring. Am J Physiol Regul Integr Comp Physiol 288(1): R127–133.PubMedGoogle Scholar
  16. Lane N, Dean W, Erhardt S, et al (2003) Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35(2): 88–93.PubMedCrossRefGoogle Scholar
  17. Neel JV (1962) Diabetes mellitus: a ‘thrifty’ genotype rendered detrimental by ‘progress’? Am J Hum Genet 14: 353–362.PubMedGoogle Scholar
  18. Ozanne SE, Hales CN (2004) Lifespan: catch-up growth and obesity in male mice. Nature 427(6973): 411–412.PubMedCrossRefGoogle Scholar
  19. Ozanne SE, Fernandez-Twinn D, Hales CN (2004) Fetal growth and adult diseases. Semin Perinatol 28(1): 81–87.PubMedCrossRefGoogle Scholar
  20. Plagemann A, Harder T, Franke K, Kohlhoff R (2002) Long-term impact of neonatal breast-feeding on body weight and glucose tolerance in children of diabetic mothers. Diabetes Care 25(1): 16–22.PubMedGoogle Scholar
  21. Rakyan VK, Chong S, Champ ME, et al (2003) Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci USA 100(5): 2538–2543.PubMedCrossRefGoogle Scholar
  22. Spotswood HT, Turner BM (2002) An increasingly complex code. J Clin Invest 110(5): 577–582.PubMedCrossRefGoogle Scholar
  23. Srinivasan M, Aalinkeel R, Song F, Patel MS (2003) Programming of islet functions in the progeny of hyperinsulinemic/obese rats. Diabetes 52(4): 984–990.PubMedGoogle Scholar
  24. Strathdee G, Brown R (2002) Epigenetic cancer therapies: DNA methyltransferase inhibitors. Expert Opin Investig Drugs 11(6): 747–754.PubMedCrossRefGoogle Scholar
  25. Waddington C (1942) Canalisation of development and inheritance of acquired characters. Nature 152: 563.Google Scholar
  26. Waterland RA, Garza C (1999) Potential mechanisms of metabolic imprinting that lead to chronic disease. Am J Clin Nutr 69(2): 179–197.PubMedGoogle Scholar
  27. Waterland RA, Jirtle RL (2003) Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23(15): 5293–5300.PubMedCrossRefGoogle Scholar
  28. Waterland RA, Jirtle RL (2004) Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition 20(1): 63–68.PubMedCrossRefGoogle Scholar
  29. Weaver IC, Cervoni N, Champagne FA, et al (2004) Epigenetic programming by maternal behavior. Nature Neuroscience 7(8): 847–854.PubMedCrossRefGoogle Scholar
  30. Whitelaw E, Martin DI (2001) Retrotransposons as epigenetic mediators of phenotypic variation in mammals. Nature Genetics 27(4): 361–365.PubMedCrossRefGoogle Scholar
  31. Xu GL, Bestor TH (1997) Cytosine methylation targetted to pre-determined sequences. Nature Genetics 17(4): 376–378.PubMedCrossRefGoogle Scholar
  32. Zhang L, Spratt SK, Liu Q, et al (2000) Synthetic zinc finger transcription factor action at an endogenous chromosomal site. Activation of the human erythropoietin gene. J Biol Chem 275(43): 33850–33860.PubMedCrossRefGoogle Scholar

Copyright information

© SSIEM and Springer 2006

Authors and Affiliations

  1. 1.Inserm Unit 383, Clinique Maurice Lamyporte 15, Hôpital Necker- Enfants MaladesParisFrance

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