School of Biological Sciences, University of Southampton, Southampton, UK.
Int J Obes (Lond). 2011 Jan;35(1):72-83. doi: 10.1038/ijo.2010.122. Epub 2010 Jun 15.
The rapid increase in incidence of obesity over the past two decades cannot be explained solely by genetic and adult lifestyle factors. There is now considerable evidence that the fetal and early postnatal environments also strongly influence the risk of developing obesity in later life. Initially, human studies showed that low birth weight was associated with an increased risk of obesity but increasingly there is evidence that overnutrition in the early life can also increase susceptibility to future obesity. These findings have now been replicated in animal models, which have shown that both maternal under- and overnutrition can induce persistent changes in gene expression and metabolism. The mechanism by which the maternal nutritional environment induces such changes is beginning to be understood and involves the altered epigenetic regulation of specific genes. In this review, we discuss the recent evidence that shows that early-life environment can induce altered epigenetic regulation leading to the induction of an altered phenotype. The demonstration of a role for altered epigenetic regulation of genes in the developmental induction of obesity opens the possibility that interventions, either through nutrition or specific drugs, may modify long-term obesity risk and combat this rapid rise in obesity.
在过去的二十年中，肥胖症的发病率迅速上升，这不能仅仅用遗传和成年生活方式因素来解释。现在有相当多的证据表明，胎儿和出生后早期的环境也强烈影响着以后生活中肥胖症的发病风险。最初，人类研究表明，低出生体重与肥胖风险增加有关，但越来越多的证据表明，生命早期的营养过剩也会增加对未来肥胖的易感性。这些发现现在已经在动物模型中得到了复制，这些模型表明，母体营养不足和营养过剩都可以诱导基因表达和代谢的持久变化。母体营养环境引起这种变化的机制开始被理解，涉及特定基因的表观遗传调控的改变。在这篇综述中，我们讨论了最近的证据，表明生命早期的环境可以诱导表观遗传调控的改变，从而导致表型的改变。基因的表观遗传调控改变在肥胖症发育过程中的作用的证明，为通过营养或特定药物干预来改变长期肥胖风险并对抗肥胖症的迅速上升提供了可能。
