下丘脑腹内侧核COUP-TFII基因在能量动态平衡中的作用

食物摄取和能量消耗是机体能量动态平衡的决定因素，受中枢神经系统（尤其是下丘脑腹内侧神经核，VMH）精细调控。然而，有关VMH核参与食物摄取和能量消耗的机理仍不清楚。申请人原实验室研究表明，COUP-TFII基因在脂肪组织参与代谢调控；申请人发现，COUP-TFII基因亦可能在中枢神经系统调控能量动态平衡，而且COUP-TFII基因特异性地在VMH神经核高表达。但是，COUP-TFII基因在VMH核的功能及作用机理尚待研究。本项目应用VMH核条件性COUP-TFII基因剔除或过表达小鼠模型，研究COUP-TFII基因如何调控食物摄取和能量消耗，解析COUP-TFII基因调控的VMH神经元通路，及VMH核神经信号与脂肪组织信号的相互作用。本项目对阐明VMH神经核对机体内部能量动态平衡的调控机制有重要理论意义，为探索肥胖症的治疗途径提供理论依据。

Food intake and energy expenditure, the key components of the energy homeostasis system, are tightly modulated by the center nervous system (CNS), especially by the ventromedial hypothalamic nucleus (VMH). Nonetheless, the molecular mechanisms how the VMH neurons participate in the regulation of the food intake and energy expenditure are still largely unclear. It has been demonstrated that COUP-TFII gene is involved in the metabolic regulation in the adipocyte tissue. Our unpublished data show that COUP-TFII gene might also regulate the energy homeostasis in the CNS, and we observed that COUP-TFII gene is preferentially expressed in the murine developing and mature VMH neurons. However, little is known about its function in the VMH nucleus. In the study, we will generate both the VMH specific conditional knockout mutant and overexpressing mutant mice of COUP-TFII gene. We are planning to investigate how COUP-TFII gene regulates the food intake and energy expenditure in the VHM nucleus, which VHM neuronal signaling pathway might be controlled by the gene, and how the VMH neuronal signals and adipocyte signals are coordinated to modulate the energy balance. Thus, our proposed study will benefit not only the understanding of the molecular mechanisms of the energy homeostasis regulation in CNS, but also the understanding of the etiology and therapy of obesity.