下丘脑CRABP1调控能量代谢的作用和分子机制研究

最近研究发现视黄酸结合蛋白1(CRABP1)在下丘脑弓状核的一些神经元中有特异性表达。目前尚无任何有关CRABP1在下丘脑中的作用和功能的研究报道。前期预实验结果显示，CRABP1特异性地在下丘脑中高表达。在高脂肪饲喂下，Crabp1基因敲除小鼠的体重和体脂率显著上升。我们推测：下丘脑中CRABP1蛋白和CRABP1表达神经元在能量代谢调控中扮演着非常重要的角色。为了验证这一假设，本项目拟开展以下研究：（1）在下丘脑弓状核中特异性敲除Crabp1基因，以阐明CRABP1在下丘脑能量调控的作用；（2）通过各种分子手段验证CRABP1神经元是否是一类新的神经元，并进一步研究CRABP1神经元在能量调控中的作用；（3）深入研究CRABP1调控能量代谢的机理。本研究成果将揭示CRABP1蛋白和CRABP1神经元在能量调控中的作用和调控机理，为肥胖等代谢病的发病病因发现新的机制和治疗靶点。

A recent study has found that retinoic acid-binding protein 1 (CRABP1) is specifically expressed in some neurons of the arcuate nucleus of the hypothalamus. However, there have been no reports on the role and function of CRABP1 in the hypothalamus. Our preliminary results showed that CRABP1 was specifically high expressed in the hypothalamus. Under high fat diet feeding condition, the body weight and body fat rate of Crabp1 knockout mice increased significantly compare to littermate controls. We speculated that CRABP1 protein and CRABP1 expression neurons in the hypothalamus play a very important role in the regulation of energy metabolism. In order to verify this hypothesis, this project intends to carry out the following research: (1) specifically knock out Crabp1 gene in the arcuate nucleus to elucidate the role of Crabp1 in hypothalamic energy regulation; (2) verify whether CRABP1 neurons are a new type of neurons and study the role of CRABP1 neurons in energy regulation; (3) In-depth study on the mechanism of CRABP1 regulating energy metabolism. The results of this study will reveal the role and regulatory mechanism of CRABP1 protein and CRABP1 neurons in energy regulation, discover new mechanisms for the pathogenesis of obesity, and provide new therapeutic targets in obesity treatment.