Columbia University, Department of Genetics and Development, Hammer Health Science Center, 701 West 168th Street, New York, NY 10032, USA.
Trends Endocrinol Metab. 2011 Sep;22(9):382-7. doi: 10.1016/j.tem.2011.04.006. Epub 2011 May 24.
Leptin exerts control over energy metabolism, reproduction and bone mass accrual, raising the question does leptin act through a common neuronal circuit to mediate these effects? Historically, the hypothalamus has been viewed as the site for leptin signaling in the brain. Recent genetic studies, however, indicate that these physiological functions, notably the regulation of appetite and bone mass accrual by leptin, take place for the most part through inhibition of serotonin (5-hydroxytryptamine) synthesis and release by brainstem neurons. Here, we review how these findings have redefined the roadmap of leptin signaling in the brain. This has led to proof-of-principle studies showing that selective inhibition of the leptin-serotonin axis is a viable therapeutic approach to treat appetite disorders.
瘦素对能量代谢、生殖和骨量积累进行控制,这就提出了一个问题:瘦素是否通过一个共同的神经元回路来发挥作用,从而介导这些效应?从历史上看,下丘脑被认为是大脑中瘦素信号传递的部位。然而,最近的遗传研究表明,这些生理功能,特别是瘦素对食欲和骨量积累的调节,主要是通过脑干神经元抑制 5-羟色胺(5-羟色胺)的合成和释放来实现的。在这里,我们回顾了这些发现如何重新定义了大脑中瘦素信号传递的路线图。这导致了原理验证研究表明,选择性抑制瘦素-5-羟色胺轴是治疗食欲障碍的一种可行的治疗方法。