Prenatal nutrition and the risk of adult obesity: Long-term effects of nutrition on epigenetic mechanisms regulating gene expression

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• 作者：Estanislau Navarro^a ; ^{enavarro@idibell.cat} ; ^{estanis.navarro@gmail.com} ; Anna N. Funtikova^b ; ^c ; ^d ; Montserrat Fí ; to^b ; ^e ; Helmut Schrö ; der^b ; ^c
• 关键词：AS-RNA ; antisense RNA ; BAT ; brown adipose tissue ; BET ; bromodomain and extraterminal ; BMI ; body mass index ; CAD ; coronary artery disease ; CVD ; cardiovascular diseases ; DHA ; docosahexaenoic acid ; DMR ; differentially-methylated region ; DNMTs ; DNA methyltransferases ; DOAD ; developmental origins of adult disease ; DWF ; Dutch Winter Famine ; EGCG ; (&minus ; )-epigallocatechin gallate ; eRNAs ; enhancer RNAs ; ERV ; endogenous retrovirus ; GEN ; genistein ; HAT ; histone acetyl transferase ; HDAC ; histone deacetyl
• 刊名：The Journal of Nutritional Biochemistry
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：39
• 期：Complete
• 页码：1-14
• 全文大小：753 K
• 卷排序：39

文摘

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.