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Amylin receptors in the lateral dorsal tegmental area regulate food intake

背侧被盖区的胰淀素受体调节食物摄入

基本信息

批准号：
9050743
负责人：
David Reiner
金额：
$ 4.31万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9050743
关键词：
Action Potentials Acute Affect Agonist Anti-Obesity Agents Appetite Depressants Area Attenuated Automobile Driving Basic Science Behavior Behavioral Behavioral Mechanisms Behavioral Model Beta Cell Binding Binding Sites Body Weight Brain Brain Stem Calcitonin Receptor Cell Nucleus Chronic Communication Complex Data Diet Dorsal Eating Endocrine Epidemic FOS gene Fatty acid glycerol esters Fiber Food Food Energy Food Intake Regulation Food Interactions Hormones Hypothalamic structure Incentives Intake Laboratories Lateral Location Measures Mediating Messenger RNA Motivation Neuroendocrinology Neurons Nucleus solitarius Obesity Pancreas Peripheral Pharmacotherapy Physiological Process Prosencephalon Proteins Public Health RNA Interference Rattus Receptor Activation Receptor Signaling Regulation Reinforcement Schedule Research Rewards Role Satiation Self Administration Self-Administered Signal Transduction Site Source Stomach Structure of area postrema Sucrose Synapses System Techniques Testing Therapeutic Tissues Ventral Tegmental Area Viral Vector Weight Gain Work amylin receptor design drug development energy balance feeding glucagon-like peptide hindbrain insight islet amyloid polypeptide motivated behavior neural circuit neurobiological mechanism neurotransmission novel obesity treatment preference public health relevance receptor expression relating to nervous system research study small hairpin RNA theories therapeutic target

项目摘要

DESCRIPTION (provided by applicant): Amylin is a pancreatic-derived hormone that acts in the CNS to reduce food intake. While historically the hypophagic effects of amylin have been attributed to processing by the area postrema, recently the ventral tegmental area (VTA), a nucleus in the mesolimbic reward system, was highlighted as a pharmacologically and physiologically relevant site of action for amylin-mediated control of energy balance and food reward. These discoveries encourage a broader assessment of the CNS circuitry mediating amylin's effects on food intake and reward. Given that the lateral dorsal tegmental area (LDTg) of the brainstem: [1] receives input from feeding-relevant nuclei of the hindbrain and forebrain, [2] binds amylin, and [3] sends input to the VTA to modulate rewarding behavior, the proposed aims will test the hypothesis that amylin receptor signaling in the LDTg is integral for the regulation of energy balance and food reward. Specifically, we will test the physiological requirement of LDTg amylin receptor signaling in regulation of energy balance, the role of LDTg amylin receptor signaling in rewarding value of food, and the potential interaction with gut-to-brain glucagon- like peptide-1 (GLP-1) within-meal satiation signaling as a putative mechanism contributing to intake suppression. Together the proposed aims will highlight the amylin receptor system, as well as LDTg neural processing as critical to the regulation of food intake and food motivated behaviors.

描述(申请人提供)：胰淀素是一种胰腺衍生的激素，作用于中枢神经系统以减少食物摄入。虽然在历史上，淀粉素的低噬作用被归因于最后区的处理，但最近，腹侧被盖区(VTA)，中脑边缘奖赏系统中的一个核心，被强调为与胰淀素介导的能量平衡和食物奖赏控制的药理和生理相关的作用场所。这些发现鼓励对调节胰淀素对食物摄取和奖励影响的中枢神经系统回路进行更广泛的评估。考虑到脑干的外侧背侧被盖区(LDTg)：[1]接受来自后脑和前脑的与摄食相关的核团的输入，[2]与胰淀素结合，[3]将输入发送到VTA以调节奖励行为，所提出的目标将检验这一假设，即LDTg中的淀粉素受体信号对于能量平衡和食物奖励的调节是不可或缺的。具体地说，我们将测试LDTg胰淀素受体信号在调节能量平衡中的生理需求，LDTg胰淀素受体信号在食物奖励价值中的作用，以及与肠到脑胰高血糖素样肽-1(GLP-1)的潜在相互作用作为促进摄入抑制的可能机制。总之，拟议的目标将强调淀粉素受体系统以及LDTg神经处理对于调节食物摄入量和食物动机行为至关重要。