A wealth of animal and human studies demonstrate that perinatal exposure to adverse metabolic conditions - be it maternal obesity, diabetes or under-nutrition - results in predisposition of offspring to develop obesity later in life. This mechanism is a contributing factor to the exponential rise in obesity rates. Increased weight gain in offspring exposed to maternal obesity is usually associated with hyperphagia, implicating altered central regulation of energy homeostasis as an underlying cause. Perinatal development of the hypothalamus (a brain region key to metabolic regulation) is plastic and sensitive to metabolic signals during this critical time window. Recent research in non-human primate and rodent models has demonstrated that exposure to adverse maternal environments impairs the development of hypothalamic structure and consequently function, potentially underpinning metabolic phenotypes in later life. This review summarizes our current knowledge of how adverse perinatal environments program hypothalamic development and explores the mechanisms that could mediate these effects.

中文翻译：

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代谢疾病的早期生命起源：控制能量稳态的下丘脑通路的发育编程

大量动物和人类研究表明，围产期暴露于不利的代谢条件——无论是母体肥胖、糖尿病还是营养不良——会导致后代在以后的生活中容易患上肥胖症。这种机制是导致肥胖率呈指数增长的一个因素。暴露于母体肥胖的后代体重增加增加通常与摄食过多有关，这表明能量稳态的中枢调节改变是潜在原因。下丘脑（代谢调节的关键大脑区域）的围产期发育是可塑性的，并且在这个关键时间窗口内对代谢信号敏感。最近对非人类灵长类动物和啮齿动物模型的研究表明，暴露于不利的母体环境会损害下丘脑结构的发育并因此损害其功能，这可能是晚年代谢表型的基础。这篇综述总结了我们目前对不良围产期环境如何影响下丘脑发育的知识，并探讨了可能介导这些影响的机制。