title: Prenatal nutrition and the risk of adult obesity: Long-term effects of nutrition on epigenetic mechanisms regulating gene expression.
abstract: Solid epidemiological evidence indicates that part of the risk of obesity in adulthood could be programmed during prenatal development by the quality of maternal nutrition. Nevertheless, the molecular mechanisms involved are mostly unknown, which hinders our capacity to develop effective intervention policies. Here, we discuss the hypothesis that mechanisms underlying prenatal programming of adult risk are epigenetic and sensitive to environmental cues such as nutrition. While the information encoded in DNA is essentially stable, regulatory epigenetic mechanisms include reversible, covalent modifications of DNA and chromatin, such as methylation, acetylation etc. It is known that dietary availability of methyl donors has an impact on the patterns of gene expression by affecting DNA methylation at regulatory regions, a likely basis for reprogramming developmental plasticity. The Agouti and Axin-fused genes, as well as the embryonic growth factor IGF2/H19 locus are examples of diet-induced modulation of phenotypic traits by affecting methylation of gene-regulatory regions. Recent work has evidenced an unsuspected role for chromatin as metabolic sensor. Chromatin is susceptible to a number of post-translational modifications that modulate gene expression, among them the GlcNAcylation of histone proteins and other epigenetic regulators. Intracellular levels of the precursor molecule UDP-GlcNAc, and hence the degree of global chromatin GlcNAcylation, depend on the energetic state of the cell, making GlcNAcylation a functional link between nutrition and regulation of gene expression. Dietary interference with these regulatory mechanisms could effectively counteract the early-life programming of adult risk.
authors.affiliation: Molecular Oncology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. Electronic address: enavarro@idibell.cat.
authors.forename: Estanislau
authors.initials: E
authors.lastname: Navarro
authors.affiliation: Cardiovascular Risk and Nutrition Research Group (CARIN), IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; CIBER Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Spain; PhD candidate, Food and Nutrition program, University of Barcelona, Spain.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Funtikova
authors.affiliation: Cardiovascular Risk and Nutrition Research Group (CARIN), IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Fíto
authors.affiliation: Cardiovascular Risk and Nutrition Research Group (CARIN), IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; CIBER Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Spain.
authors.forename: Helmut
authors.initials: H
authors.lastname: Schröder
mesh_terms: D000328:Adult; D054366:Agouti Signaling Protein / Q000235:genetics; D001682:Biological Availability; D002843:Chromatin / Q000235:genetics; D004032:Diet; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D044342:Malnutrition / Q000473:pathology; D054647:Nutrigenomics; D009765:Obesity / Q000235:genetics*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena; D012307:Risk Factors
chemical_list: D054366:Agouti Signaling Protein; D002843:Chromatin; C035170:IGF2 protein, human; D007335:Insulin-Like Growth Factor II
keywords: Epigenetic memory; Gestational programming; Nutrient sensors; Nutrition; O-GlcNAcylation; Regulatory exhaustion