This review analyzes the published evidence regarding maternal factors that influence the developmental programming of long-term adiposity in humans and animals via the central nervous system (CNS). We describe the physiological outcomes of perinatal under- and overfeeding and explore potential mechanisms that may mediate the impact of such exposures on the development of feeding circuits within the CNS-including the influences of metabolic hormones and epigenetic changes. The perinatal environment, reflective of maternal nutritional status, contributes to the programming of offspring adiposity. The in utero and early postnatal periods represent critically sensitive developmental windows during which the hormonal and metabolic milieu affects the maturation of the hypothalamus. Maternal hyperglycemia is associated with increased transfer of glucose to the fetus driving fetal hyperinsulinemia. Elevated fetal insulin causes increased adiposity and consequently higher fetal circulating leptin concentration. Mechanistic studies in animal models indicate important roles of leptin and insulin in central and peripheral programming of adiposity, and suggest that optimal concentrations of these hormones are critical during early life. Additionally, the environmental milieu during development may be conveyed to progeny through epigenetic marks and these can potentially be vertically transmitted to subsequent generations. Thus, nutritional and metabolic/endocrine signals during perinatal development can have lifelong (and possibly multigenerational) impacts on offspring body weight regulation.

中文翻译：

---

肥胖的神经发育编程：对肥胖风险的影响。

这篇综述分析了已发表的关于通过中枢神经系统（CNS）影响人类和动物长期肥胖发育规划的母体因素的证据。我们描述了围产期喂养不足和过度喂养的生理结果，并探讨了可能介导此类暴露对中枢神经系统内喂养回路发育的影响的潜在机制，包括代谢激素和表观遗传变化的影响。反映母亲营养状况的围产期环境有助于后代肥胖的规划。子宫内和产后早期是极其敏感的发育窗口，在此期间，激素和代谢环境影响下丘脑的成熟。母亲高血糖与葡萄糖向胎儿转移增加导致胎儿高胰岛素血症有关。胎儿胰岛素升高会导致肥胖增加，从而导致胎儿循环瘦素浓度升高。动物模型的机制研究表明，瘦素和胰岛素在中枢和外周肥胖编程中发挥着重要作用，并表明这些激素的最佳浓度在生命早期至关重要。此外，发育过程中的环境环境可能通过表观遗传标记传递给后代，并且这些可能会垂直传递给后代。因此，围产期发育期间的营养和代谢/内分泌信号可能对后代体重调节产生终生（可能是多代）影响。