Epigenetic processes which include DNA methylation, histone modification and miRNAs are integral in determining when and where specific genes are expressed. There is now increasing evidence that the epigenome is susceptible to a variety of environmental cues, such as nutrition, during specific periods of development. The changes induced by early-life nutrition may reflect an adaptive response of the foetus to environmental cues acting through the process of developmental plasticity. This may allow an organism to adjust its developmental programme resulting in long-term changes in its metabolism and physiology in order to be better matched to the future environment. However, when the future environment lies outside the anticipated range, metabolic and homoeostatic capacity will be mismatched with the environment and that individual will be at increased risk of developing a range of non-communicable diseases. Thus the environmental regulation of epigenetic processes is a central component in the developmental origins of non-communicable diseases and our understanding of these processes is, therefore, critical both for the identification of individuals at risk and for the development of new intervention strategies.

1.
Godfrey KM, Barker DJ: Fetal programming and adult health. Public Health Nutr 2001;4:611–624.
2.
Armitage JA, Taylor PD, Poston L: Experimental models of developmental programming: consequences of exposure to an energy rich diet during development. J Physiol 2005;565:3–8.
3.
Bertram CE, Hanson MA: Animal models and programming of the metabolic syndrome. Br Med Bull 2001;60:103–121.
4.
Barker DJ, Osmond C: Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1986;1:1077–1081.
5.
Curhan GC, Willett WC, Rimm EB, Spiegelman D, Ascherio AL, Stampfer MJ: Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation 1996;94:3246–3250.
6.
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;308:942–945.
7.
Painter RC, Roseboom TJ, Bleker OP: Prenatal exposure to the Dutch famine and disease in later life: an overview. Reprod Toxicol 2005;20:345–352.
8.
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;26:213–221.
9.
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;196:322–328.
10.
Villamor E, Cnattingius S: Interpregnancy weight change and risk of adverse pregnancy outcomes: a population-based study. Lancet 2006;368:1164–1170.
11.
Kral JG, Biron S, Simard S, Hould FS, Lebel S, Marceau S, Marceau P: 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–e1649.
12.
Langley-Evans SC, Phillips GJ, Jackson AA: In utero exposure to maternal low protein diets induces hypertension in weanling rats, independently of maternal blood pressure changes. Clin Nutr 1994;13:319–324.
13.
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;92:513–520.
14.
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;30:729–738.
15.
Lucas A, Baker BA, Desai M, Hales CN: Nutrition in pregnant or lactating rats programs lipid metabolism in the offspring. Br J Nutr 1996;76:605–612.
16.
Burdge GC, Slater-Jefferies JL, Grant RA, Chung WS, West AL, Lillycrop KA, Hanson MA, Calder PC: Sex, but not maternal protein or folic acid intake, determines the fatty acid composition of hepatic phospholipids, but not of triacylglycerol, in adult rats. Prostaglandins Leukot Essent Fatty Acids 2008;78:73–79.
17.
Torrens C, Hanson MA, Gluckman PD, Vickers MH: Maternal undernutrition leads to endothelial dysfunction in adult male rat offspring independent of postnatal diet. Br J Nutr 2009;101:27–33.
18.
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.
19.
Langley-Evans SC, Sculley DV: Programming of hepatic antioxidant capacity and oxidative injury in the ageing rat. Mech Ageing Dev 2005;126:804–812.
20.
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;40:438–443.
21.
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 11β-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology 2001;142:2841–2853.
22.
Burns SP, Desai M, Cohen RD, Hales CN, Iles RA, Germain JP, Going TCH, Bailey RA: 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;100:1768–1774.
23.
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;11:461–468.
24.
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;135:1382–1386.
25.
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;97:1064–1073.
26.
Gluckman PD, Lillycrop KA, Vickers MH, Pleasants AB, Phillips ES, Beedle AS, Burdge GC, Hanson MA: Metabolic plasticity during mammalian development is directionally dependent on early nutritional status. Proc Natl Acad Sci USA 2007;104:12796–12800.
27.
Carone BR, Fauquier L, Habib N, Shea JM, Hart CE, Li R, Bock C, Li C, Gu H, Zamore PD, Meissner A, Weng Z, Hofmann HA, Friedman N, Rando OJ: Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 2010;143:1084–1096.
28.
Lillycrop KA, Rodford J, Garratt ES, Slater-Jefferies JL, Godfrey KM, Gluckman PD, Hanson MA, Burdge GC: Maternal protein restriction with or without folic acid supplementation during pregnancy alters the hepatic transcriptome in adult male rats. Br J Nutr 2010;103:1711–1719.
29.
Gheorghe CP, Goyal R, Holweger JD, Longo LD: Placental gene expression responses to maternal protein restriction in the mouse. Placenta 2009;30:411–417.
30.
Samuelsson AM, Matthews PA, Argenton M, Christie MR, McConnell JM, Jansen EH, Piersma AH, Ozanne SE, Twinn DF, Remacle C, Rowlerson A, Poston L, Taylor PD: Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension 2008;51:383–392.
31.
Korotkova M, Gabrielsson BG, Holmang A, Larsson BM, Hanson LA, Strandvik B: Gender-related long-term effects in adult rats by perinatal dietary ratio of n-6/n-3 fatty acids. Am J Physiol Regul Integr Comp Physiol 2005;288:R575–R579.
32.
Kozak R, Burlet A, Burlet C, Beck B: Dietary composition during fetal and neonatal life affects neuropeptide Y functioning in adult offspring. Brain Res Dev Brain Res 2000;125:75–82.
33.
Ng SF, Lin RC, Laybutt DR, Barres R, Owens JA, Morris MJ: Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 2010;467:963–966.
34.
Khan IY, Dekou V, Douglas G, Jensen R, Hanson MA, Poston L, Taylor PD: A high-fat diet during rat pregnancy or suckling induces cardiovascular dysfunction in adult offspring. Am J Physiol Regul Integr Comp Physiol 2005;288:R127–R133.
35.
Plagemann A, Heidrich I, Gotz F, Rohde W, Dorner G: Obesity and enhanced diabetes and cardiovascular risk in adult rats due to early postnatal overfeeding. Exp Clin Endocrinol 1992;99:154–158.
36.
Schmidt I, Fritz A, Scholch C, Schneider D, Simon E, Plagemann A: The effect of leptin treatment on the development of obesity in overfed suckling Wistar rats. Int J Obes Relat Metab Disord 2001;25:1168–1174.
37.
Davidowa H, Plagemann A: Decreased inhibition by leptin of hypothalamic arcuate neurons in neonatally overfed young rats. Neuroreport 2000;11:2795–2798.
38.
Plagemann A, Harder T, Rake A, Melchior K, Rohde W, Dorner G: Increased number of galanin-neurons in the paraventricular hypothalamic nucleus of neonatally overfed weanling rats. Brain Res 1999;818:160–163.
39.
Gluckman PD, Hanson MA: Developmental origins of disease paradigm: a mechanistic and evolutionary perspective. Pediatr Res 2004;56:311–317.
40.
Norman JF, LeVeen RF: Maternal atherogenic diet in swine is protective against early atherosclerosis development in offspring consuming an atherogenic diet post-natally. Atherosclerosis 2001;157:41–47.
41.
Khan I, Dekou V, Hanson M, Poston L, Taylor P: Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring. Circulation 2004;110:1097–1102.
42.
Gluckman PD, Hanson MA: The Fetal Matrix: Evolution, Development and Disease. Cambridge, Cambridge University Press, 2005.
43.
Bird A: The essentials of DNA methylation. Cell 1992;70:5–8.
44.
Bird A: DNA methylation patterns and epigenetic memory. Genes Dev 2002;16:6–21.
45.
Razin A, Szyf M: DNA methylation patterns. Formation and function. Biochim Biophys Acta 1984;782:331–342.
46.
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;278:4035–4040.
47.
Turner BM: Histone acetylation and an epigenetic code. Bioessays 2000;22:836–845.
48.
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;277:11621–11624.
49.
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;410:116–120.
50.
Kuehbacher A, Urbich C, Dimmeler S: Targeting microRNA expression to regulate angiogenesis. Trends Pharmacol Sci 2008;29:12–15.
51.
Kim DH, Saetrom P, Snove O Jr, Rossi JJ: MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc Natl Acad Sci USA 2008;105:16230–16235.
52.
Bayne EH, Allshire RC: RNA-directed transcriptional gene silencing in mammals. Trends Genet 2005;21:370–373.
53.
Dean W, Santos F, Reik W: Epigenetic reprogramming in early mammalian development and following somatic nuclear transfer. Semin Cell Dev Biol 2003;14:93–100.
54.
Reik W: Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 2007;447:425–432.
55.
Reik W, Dean W, Walter J: Epigenetic reprogramming in mammalian development. Science 2001;293:1089–1093.
56.
Mathers JC: Nutritional modulation of ageing: genomic and epigenetic approaches. Mech Ageing Dev 2006;127:584–589.
57.
Doherty AS, Mann MR, Tremblay KD, Bartolomei MS, Schultz RM: Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo. Biol Reprod 2000;62:1526–1535.
58.
Khosla S, Dean W, Reik W, Feil R: Culture of preimplantation embryos and its long-term effects on gene expression and phenotype. Hum Reprod Update 2001;7:419–427.
59.
Orstavik KH, Eiklid K, van der Hagen CB, Spetalen S, Kierulf K, Skjeldal O, Buiting K: Another case of imprinting defect in a girl with Angelman syndrome who was conceived by intracytoplasmic semen injection. Am J Hum Genet 2003;72:218–219.
60.
Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ: Epigenetic programming by maternal behavior. Nat Neurosci 2004;7:847–854.
61.
Pham TD, MacLennan NK, Chiu CT, Laksana GS, Hsu JL, Lane RH: Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full-term IUGR rat kidney. Am J Physiol Regul Integr Comp Physiol 2003;285:R962–R970.
62.
Maleszka R: Epigenetic integration of environmental and genomic signals in honey bees. Epigenetics 2008;3:188–192.
63.
Kucharski R, Maleszka J, Foret S, Maleszka R: Nutritional control of reproductive status in honeybees via DNA methylation. Science 2008;319:1827–1830.
64.
Wolff GL, Kodell RL, Moore SR, Cooney CA: Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J 1998;12:949–957.
65.
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 PPARα promoter of the offspring. Br J Nutr 2008;100:278–282.
66.
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;100:520–526.
67.
Plagemann A, Harder T, Brunn M, Harder A, Roepke K, Wittrock-Staar M, Ziska T, Schellong K, Rodekamp E, Melchior K, Dudenhausen JW: Hypothalamic proopiomelanocortin promoter methylation becomes altered by early overfeeding: an epigenetic model of obesity and the metabolic syndrome. J Physiol 2009;587:4963–4976.
68.
Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, Slagboom PE, Lumey LH: Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA 2008;105:17046–17049.
69.
Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD, Slagboom PE, Heijmans BT: DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet 2009;18:4046–4053.
70.
Steegers-Theunissen RP, Obermann-Borst SA, Kremer D, Lindemans J, Siebel C, Steegers EA, Slagboom PE, Heijmans BT: Periconceptional maternal folic acid use of 400 µg per day is related to increased methylation of the IGF2 gene in the very young child. PLoS One 2009;4:e7845.
71.
Chiang PK, Gordon RK, Tal J, Zeng GC, Doctor BP, Pardhasaradhi K, McCann PP: S-Adenosylmethionine and methylation. FASEB J 1996;10:471–480.
72.
Petrie L, Duthie SJ, Rees WD, McConnell JM: Serum concentrations of homocysteine are elevated during early pregnancy in rodent models of fetal programming. Br J Nutr 2002;88:471–477.
73.
James SJ, Melnyk S, Pogribna M, Pogribny IP, Caudill MA: Elevation in S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology. J Nutr 2002;132:2361S–2366S.
74.
Jackson-Grusby L, Beard C, Possemato R, Tudor M, Fambrough D, Csankovszki G, Dausman J, Lee P, Wilson C, Lander E, Jaenisch R: Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nat Genet 2001;27:31–39.
75.
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.
76.
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;25:269–277.
77.
Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van EA, Bernard D, Vanderwinden JM, Bollen M, Esteller M, Di CL, de LY, Fuks F: The Polycomb group protein EZH2 directly controls DNA methylation. Nature 2006;439:871–874.
78.
Park JH, Stoffers DA, Nicholls RD, Simmons RA: Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest 2008;118:2316–2324.
79.
Zhang J, Zhang F, Didelot X, Bruce KD, Cagampang FR, Vatish M, Hanson M, Lehnert H, Ceriello A, Byrne CD: 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 2009;10:478.
80.
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: Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes 2011;60:1528–1534.
81.
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;99:540–549.
82.
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;139:1054–1060.
83.
Waterland RA, Travisano M, Tahiliani KG, Rached MT, Mirza S: Methyl donor supplementation prevents transgenerational amplification of obesity. Int J Obes (Lond) 2008;32:1373–1379.
84.
Vickers MH, Gluckman PD, Coveny AH, Hofman PL, Cutfield WS, Gertler A, Breier BH, Harris M: Neonatal leptin treatment reverses developmental programming. Endocrinology 2005;146:4211–4216.
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