Bouret S G, Simerly R B
Neuroscience Program, The Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA.
Clin Genet. 2006 Oct;70(4):295-301. doi: 10.1111/j.1399-0004.2006.00684.x.
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.
下丘脑在食物摄入和体重调节中起着关键作用，最近的研究确定了下丘脑的一个核心神经回路，该回路似乎介导了脂肪细胞衍生激素瘦素对进食和葡萄糖稳态的许多影响。然而，直到最近，人们对这些关键通路的发育了解甚少。这篇综述总结了下丘脑弓状核“代谢”投射出生后发育的最新进展。主要在小鼠中积累的证据表明，这些神经回路在出生后发育，直到出生后第二周在结构和功能上都仍不成熟。最近的研究已经开始确定调控这些通路发育的线索，瘦素似乎在调节食物摄入和肥胖的下丘脑回路发育中发挥关键的神经营养作用。瘦素的神经发育作用似乎特别局限于一个与瘦素自然升高相吻合的新生儿关键期。此外，出生后瘦素升高的时间和幅度对生命后期的正常体重调节和葡萄糖稳态有重要影响。最终，这些数据有望为围产期营养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。
