Leptin and Insulin Responses in Hypothalamic NPY Neurons

下丘脑 NPY 神经元中的瘦素和胰岛素反应

基本信息

批准号：
8726289
负责人：
Christopher Javadi
金额：
$ 1.28万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2013-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8726289
关键词：
ART protein Ablation Acute Adult Automobile Driving Binding Blood Glucose Body Weight Brain Brain region Catalytic Domain Child Cranial Nerves Diet Disease Eating Endogenous Factors Energy Intake Energy Metabolism Equilibrium Event Fasting Fatty acid glycerol esters Feedback Feeding behaviors Food Energy Frequencies Genes Genetic Glucose Homeostasis Hormonal Hormones Human Hypertension Hypothalamic structure Insulin Insulin Receptor Leptin Ligands Liver diseases Mammals Measures Mediating Melanocortin 4 Receptor Modeling Mus Neuraxis Neurons Neuropeptides Neurotransmitters Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Obesity Pathway interactions Peptides Peripheral Peripheral Nerves Preparation Prevalence Pro-Opiomelanocortin Production Reporter Resistance Rodent Role Signal Transduction Slice Structure of nucleus infundibularis hypothalami Synapses System Techniques Testing Wood material agouti protein alpha-Melanocyte stimulating hormone blood glucose regulation energy balance feeding gamma-Aminobutyric Acid glucose tolerance insight insulin tolerance leptin receptor neural circuit neuropeptide Y neurotransmitter release optogenetics overexpression relating to nervous system research study response transmission process vesicular GABA transporter

项目摘要

DESCRIPTION (provided by applicant): Obesity is fundamentally a disorder of energy balance. Adult body weight is normally maintained within a narrow range by neural and hormonal circuits which act to balance energy intake and expenditure. To accomplish this balancing act, the central nervous system senses and responds to changes in circulating metabolites, such as glucose and free fatty acids, and hormones, such as insulin and leptin. In humans and other mammals, these peripheral signals are integrated by neural circuits in the hypothalamus, which then coordinate responses via projections to other brain regions. One such feedback circuit, the melanocortin circuit in the arcuate nucleus of the hypothalamus, consists of neuropeptide Y (NPY)-expressing neurons, which promote feeding and decrease energy expenditure, and pro-opiomelanocortin (POMC)-expressing neurons, which inhibit feeding and increase energy expenditure. However, the downstream events of hormone sensing in NPY neurons are presently unclear. This project will investigate the acute changes in electrical activity of NPY neurons in response to leptin and insulin and the intracellular signalin pathway that may mediate these effects. Determining these pathways may reveal insights into how resistance to these signals occurs in obesity and type 2 diabetes.

描述（由申请人提供）：肥胖从根本上来说是一种能量平衡紊乱。成人体重通常通过神经和激素回路维持在一个狭窄的范围内，这些回路起到平衡能量摄入和消耗的作用。为了实现这种平衡作用，中枢神经系统感知循环代谢物（例如葡萄糖和游离脂肪酸）以及激素（例如胰岛素和瘦素）的变化并做出反应。在人类和其他哺乳动物中，这些外周信号由下丘脑的神经回路整合，然后通过投射到其他大脑区域来协调反应。其中一种反馈回路是下丘脑弓状核中的黑皮质素回路，由表达神经肽 Y (NPY) 的神经元和表达阿片黑皮质素原 (POMC) 的神经元组成，前者促进进食并减少能量消耗，后者抑制进食和减少能量消耗。增加能量消耗。然而，NPY 神经元激素感应的下游事件目前尚不清楚。该项目将研究 NPY 神经元响应瘦素和胰岛素的电活动的急性变化，以及可能介导这些效应的细胞内信号通路。确定这些途径可能会揭示肥胖和 2 型糖尿病中对这些信号的抵抗如何发生的见解。