Leptin and Insulin Signaling in SF1 Neurons and Energy Homeostasis

描述(申请人提供)：下丘脑中的瘦素和胰岛素信号是葡萄糖和能量消耗的中央调节的关键。特别重要的是下丘脑腹内侧(VMH)的PI3K信号，这是大脑中调节交感神经流出的中心区域。我们的初步结果揭示了PI3K信号的复杂性，有多个亚基，每个亚基负责能量稳态的不同方面。在这一应用中，我们开发了新的小鼠遗传学工具来研究解剖识别的SF1神经元中PI3K途径和瘦素信号的生理需求。此外，我们将研究这些途径是如何汇聚在一起来调节运动的有益效果的。总之，这些研究将增加我们对能量平衡的生物控制以及它与运动的关系的理解，并将为新批准的减肥药物的有效性和安全性提供机械性的见解。

DESCRIPTION (provided by applicant): Leptin and insulin signaling in the hypothalamus are key to the central regulation of glucose and energy expenditure. Of particular importance is PI3K signaling in the ventromedial hypothalamus (VMH), a brain region central for the regulation of sympathetic outflow. Our preliminary results reveal the complex nature of PI3K signaling, with multiple subunits, each responsible for different aspects of energy homeostasis. Within this application we have developed novel mouse genetic tools to study the physiological requirements for the PI3K pathway and leptin signaling in anatomically identified SF1 neurons. Furthermore, we will examine how these pathways converge to mediate the beneficial effects of exercise. Together, these studies will increase our understanding of the biological control of energy balance, how it relates to exercise, and will provide mechanistic insights to the effectiveness and safety of newly approved anti-obesity drugs.