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Leptin and Insulin Signaling in SF1 Neurons and Energy Homeostasis

SF1 神经元中的瘦素和胰岛素信号传导与能量稳态

基本信息

批准号：
10341072
负责人：
JOEL K. ELMQUIST
金额：
$ 40.96万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-08 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10341072
关键词：
Affect Agonist Binding Body Composition Body Weight Brain CNR1 gene Cannabinoids Cell Nucleus Clinical Development Diabetes Mellitus Endocannabinoids Equilibrium Exercise Funding Genetic Genetic Transcription Glucose Goals Hand High Fat Diet Homeostasis Hypothalamic structure Impairment Insulin Resistance Investigation Knock-out Knockout Mice Leptin Lipids Mediating Metabolic Metabolic Diseases Modeling Mus Neurons Non-Insulin-Dependent Diabetes Mellitus Obesity Pharmaceutical Preparations Phenocopy Population Predisposition Public Health Receptor Gene Regulation Role SF1 Site Stimulus Sympathetic Nervous System System Temperature Testing Tissues base blood glucose regulation combat diet-induced obesity effective therapy endogenous cannabinoid system energy balance exercise training feeding improved insight insulin sensitivity insulin signaling mouse model novel novel therapeutic intervention novel therapeutics prevent receptor expression response side effect transcription factor

项目摘要

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.

摘要由CB1R和脂源性内源性大麻素分子组成的内源性大麻素系统，已被证明对糖尿病和肥胖症的发展有重大贡献。尽管CB1R逆势激动剂在改善胰岛素敏感性和预防饮食引起的肥胖方面有效，这些药物与CB1R在中枢神经系统和外围地区的广泛分布有关的严重副作用。本应用的目的是研究CB1Rs在腹内侧区SF1神经元中的作用下丘脑调节能量动态平衡。我们还将研究这部分神经元是否负责与CB1R反向激动剂相关的代谢改善。我们期待着我们的结果研究将为开发抗击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。