Developmental programming of hypothalamic feeding circuits
Developmental programming of hypothalamic feeding circuits
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DOI：
10.1111/j.1399-0004.2006.00684.x
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发表时间：
2006-10-01
影响因子：
3.5
通讯作者：
Simerly, R. B.
中科院分区：
文献类型：
--
作者：
Bouret, S. G.;Simerly, R. B.
下丘脑在食物摄入和体重的调节中起着至关重要的作用，最近的工作已经确定了下丘脑的核心回路，该回路似乎介导脂肪细胞来源的激素瘦素对进食和葡萄糖稳态的许多影响。然而，直到最近，人们对这些关键途径的发展知之甚少。这篇综述总结了有关下丘脑弓状核产后“代谢”投射发育的最新进展。主要在小鼠身上积累的证据表明，这些回路在出生后发育，并且在结构和功能上保持不成熟，直到生命的第二周。最近的研究已经开始确定控制这些途径发展的线索，瘦素似乎在调节食物摄入和肥胖的下丘脑回路的发展中发挥着至关重要的神经营养作用。瘦素的神经发育作用似乎特别局限于新生儿关键期，该时期与瘦素自然发生的激增相一致。此外，产后瘦素激增的时间和幅度对于以后生活中的正常体重调节和葡萄糖稳态具有重要影响。最终，这些数据有望为围产期营养的改变可能对后代体重调节和肥胖产生长期影响的机制提供新的见解。
The hypothalamus plays a critical role in the regulation of food intake and body weight, and recent work has defined a core circuitry in the hypothalamus that appears to mediate many of the effects of the adipocyte-derived hormone leptin on feeding and glucose homeostasis. However, until recently, little was known about the development of these critical pathways. This review summarizes recent advances regarding the post-natal development of 'metabolic' projections from the arcuate nucleus of the hypothalamus. Evidence accumulated primarily in mice indicates that these circuits develop after birth and remain both structurally and functionally immature until the second week of life. Recent studies have begun to identify cues governing development of these pathways, and leptin appears to play a crucial neurotrophic role in the development of the hypothalamic circuits regulating food intake and adiposity. The neurodevelopmental actions of leptin appear specifically to be restricted to a neonatal critical period that coincides with the naturally occurring surge in leptin. In addition, the timing and amplitude of the post-natal leptin surge has important consequences for normal body weight regulation and glucose homeostasis later in life. Ultimately, these data promise to provide new insight into the mechanisms by which alteration of perinatal nutrition may have long-term consequences on body weight regulation and adiposity in the offspring.