title: The early programming of metabolic health: is epigenetic setting the missing link?
abstract: Adult health is dependent, in part, on maternal nutrition and growth during early life, which may independently affect insulin sensitivity, body composition, and overall energy homeostasis. Since the publication of the "thrifty phenotype hypothesis" by Hales and Barker (Diabetologia 1992;35:595-601), animal experiments have focused on establishing the mechanisms involved, which include changes in fetal cortisol, insulin, and leptin secretion or sensitivity. Intrauterine growth retardation can be induced by either prolonged modest changes in maternal diet or by more severe changes in uterine blood supply near to term. These contrasting challenges result in different amounts of cellular stress in the offspring. In addition, shifts in the transcriptional activity of DNA may produce sustained metabolic adaptations. Within tissues and organs that control metabolic homeostasis (eg, hypothalamus, adipose tissue, stomach, skeletal muscle, and heart), a range of phenotypes can be induced by sustained changes in maternal diet via modulation of genes that control DNA methylation and by histone acetylation, which suggests epigenetic programming. We now need to understand how changes in maternal diet affect DNA and how they are conserved on exposure to oxidative stress. A main challenge will be to establish how the dietary environment interacts with the programmed phenotype to trigger the development of metabolic disease. This may aid in the establishment of nutrigenomic strategies to prevent the metabolic syndrome.
authors.affiliation: Early Life Nutrition Research Unit, Academic Division of Child Health, and Nottingham Respiratory Medicine Biomedical Research Unit, School of Clinical Sciences, University Hospital Nottingham, Nottingham, United Kingdom.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Sebert
authors.forename: Don
authors.initials: D
authors.lastname: Sharkey
authors.forename: Helen
authors.initials: H
authors.lastname: Budge
authors.forename: Michael E
authors.initials: ME
authors.lastname: Symonds
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000818:Animals; D001823:Body Composition; D019175:DNA Methylation / Q000235:genetics; D004032:Diet; D004734:Energy Metabolism; D044127:Epigenesis, Genetic; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006706:Homeostasis; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D020738:Leptin / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008659:Metabolic Diseases / Q000196:embryology* / Q000235:genetics; D023421:Models, Animal; D018384:Oxidative Stress; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats
chemical_list: D007328:Insulin; D020738:Leptin; D006854:Hydrocortisone