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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：
10091429
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 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10091429
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.

抽象的内源性大麻素系统，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着影响。虽然CB1R逆激动剂可有效提高胰岛素敏感性并防止饮食引起的肥胖，这些药物具有与中枢神经系统和外周广泛分布的 CB1R 相关的严重副作用。本应用的目的是研究 CB1R 在腹内侧 SF1 神经元中的作用下丘脑调节能量稳态。我们还将检查这部分神经元是否负责与 CB1R 反向激动剂相关的代谢改善。我们预计我们的结果研究将为开发对抗代谢疾病的有效疗法提供新的见解同时规避潜在的副作用。