Leinninger G M, Myers M G
Division of Metabolism, Endocrinology and Diabetes, Department of Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0678, USA.
Acta Physiol (Oxf). 2008 Jan;192(1):49-59. doi: 10.1111/j.1748-1716.2007.01784.x.
The adipose tissue-derived hormone, leptin, acts via its receptor (LRb) in the brain to regulate energy balance and neuroendocrine function. In order to understand leptin action we have explored the physiological function of LRb signalling pathways, defining important roles for signal transducer and activator of transcription-3 (STAT3) in positive signalling and for LRbTyr(985)-mediated feedback inhibition in leptin signal attenuation. As the cells on which leptin acts are not homogeneous, but rather represent a broadly distributed network of neurones with divergent projections and functions, it is also crucial to consider how each of these populations responds to LRb signals to contribute to leptin action. While well-known LRb-expressing neurones within the arcuate nucleus of the hypothalamus mediate crucial effects on satiety and energy expenditure, other populations of LRb-expressing neurones in the ventral tegmental area and elsewhere likely control the mesolimbic dopamine system. Additional populations of LRb-expressing neurones likely contribute to other aspects of neuroendocrine regulation. It will be important to define the molecular mechanisms by which leptin acts to regulate neurophysiology in each of these LRb-expressing neural populations in order to understand the totality of leptin action.
脂肪组织衍生的激素瘦素通过其在大脑中的受体（LRb）发挥作用，以调节能量平衡和神经内分泌功能。为了了解瘦素的作用，我们探索了LRb信号通路的生理功能，确定了信号转导和转录激活因子3（STAT3）在正向信号传导中的重要作用，以及LRbTyr(985)介导的反馈抑制在瘦素信号衰减中的作用。由于瘦素作用的细胞并非同质，而是代表了一个广泛分布的神经元网络，其投射和功能各不相同，因此考虑这些细胞群体中的每一个如何对LRb信号作出反应以促成瘦素作用也至关重要。虽然下丘脑弓状核内众所周知的表达LRb的神经元对饱腹感和能量消耗起着关键作用，但腹侧被盖区及其他部位的其他表达LRb的神经元群体可能控制中脑边缘多巴胺系统。其他表达LRb的神经元群体可能对神经内分泌调节的其他方面也有贡献。为了理解瘦素作用的全貌，确定瘦素在这些表达LRb的神经群体中调节神经生理学的分子机制将非常重要。
