Leptin and Insulin Signaling in SF1 Neurons and Energy Homeostasis

摘要 内源性大麻素系统由CB1R和脂质衍生的内源性大麻素分子组成， 已被证明对糖尿病和肥胖症的发展有显著贡献。虽然CB1R逆 激动剂在改善胰岛素敏感性和防止饮食诱导的肥胖方面是有效的，这些药物 具有与CNS和外周中CB1R的广泛分布相关的严重副作用。 本申请的目的是研究CB1受体在腹内侧核SF1神经元中的作用。 下丘脑调节能量平衡。我们还将研究这个神经元子集是否负责 与CB1R反向激动剂相关的代谢改善。我们预计结果从我们的 这项研究将为开发对抗代谢性疾病的有效疗法提供新的见解 同时避免潜在的副作用

Abstract The endocannabinoid system, consisting of the CB1R and lipid derived endogenous cannabinoid molecules, has been shown to significantly contribute to the development of diabetes and obesity. Although CB1R inverse agonists are effective at improving insulin sensitivity and protecting against diet induced obesity, these drugs have severe side effects associated with the widespread distribution of CB1Rs in the CNS and the periphery. The goal of this application is to investigate the role of CB1Rs in the SF1 neurons of the ventromedial hypothalamus to regulate energy homeostasis. We will also examine if this subset of neurons is responsible for the metabolic improvements associated with CB1R inverse agonists. We anticipate the results from our investigation will provide novel insight to the development of effective therapies to combat metabolic disease while circumventing potential side effects.