Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires, National Council of Scientific and Technological Research CONICET, Ciudad Autónoma de Buenos Aires, Argentina.
Pediatr Res. 2013 Apr;73(4 Pt 2):531-42. doi: 10.1038/pr.2013.2. Epub 2013 Jan 11.
A growing body of evidence supports the notion that epigenetic changes such as DNA methylation and histone modifications, both involving chromatin remodeling, contribute to fetal metabolic programming. We use a combination of gene-protein enrichment analysis resources along with functional annotations and protein interaction networks for an integrative approach to understanding the mechanisms underlying fetal metabolic programming. Systems biology approaches suggested that fetal adaptation to an impaired nutritional environment presumes profound changes in gene expression that involve regulation of tissue-specific patterns of methylated cytosine residues, modulation of the histone acetylation-deacetylation switch, cell differentiation, and stem cell pluripotency. The hypothalamus and the liver seem to be differently involved. In addition, new putative explanations have emerged about the question of whether in utero overnutrition modulates fetal metabolic programming in the same fashion as that of a maternal environment of undernutrition, suggesting that the mechanisms behind these two fetal nutritional imbalances are different. In conclusion, intrauterine growth restriction is most likely to be associated with the induction of persistent changes in tissue structure and functionality. Conversely, a maternal obesogenic environment is most probably associated with metabolic reprogramming of glucose and lipid metabolism, as well as future risk of metabolic syndrome (MS), fatty liver, and insulin (INS) resistance.
越来越多的证据支持这样一种观点，即表观遗传变化（如涉及染色质重塑的 DNA 甲基化和组蛋白修饰）有助于胎儿代谢编程。我们使用基因-蛋白质富集分析资源以及功能注释和蛋白质相互作用网络的组合，对胎儿代谢编程的机制进行综合分析。系统生物学方法表明，胎儿对受损营养环境的适应需要涉及调节组织特异性甲基化胞嘧啶残基模式、调节组蛋白乙酰化-去乙酰化开关、细胞分化和干细胞多能性的基因表达的深刻变化。下丘脑和肝脏似乎有不同的参与。此外，关于宫内营养过剩是否以与母体营养不良环境相同的方式调节胎儿代谢编程的问题出现了新的假设性解释，这表明这两种胎儿营养失衡背后的机制是不同的。总之，宫内生长受限很可能与组织结构和功能的持久变化有关。相反，母亲肥胖的环境很可能与葡萄糖和脂质代谢的代谢重编程以及未来代谢综合征（MS）、脂肪肝和胰岛素（INS）抵抗的风险有关。
