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Brain integration of adiposity and satiety signals in the control of food intake

大脑整合肥胖和饱腹感信号来控制食物摄入

基本信息

批准号：
8119759
负责人：
Diana L Williams
金额：
$ 24.65万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8119759
关键词：
Accounting Address Adipose tissue Agonist Animals Anorexia Area Award Behavioral Biological Biological Factors Body Weight Body Weight decreased Body fat Brain Brain Stem Brain region Cell Nucleus Cells Cholecystokinin Cholecystokinin A Receptor Cholecystokinin Receptor Complex Data Defect Detection Devazepide Development Diet Dorsal Dose Eating Enteroendocrine Cell Exhibits Experimental Models FOS gene Fasting Fat-Restricted Diet Fatty acid glycerol esters Food Food Intake Regulation Gastrointestinal tract structure Gene Mutation Genetic Glucagon Goals Hormones Human Hyperphagia Hypothalamic structure Infusion procedures Ingestion Injection of therapeutic agent Intake Intraperitoneal Injections Laboratories Lead Leptin Leptin resistance Light Maintenance Mediating Mediator of activation protein Mentors Metabolic Metabolic Diseases Microinjections Modeling Mus Nature Neural Pathways Neuraxis Neurons Non-Insulin-Dependent Diabetes Mellitus Nucleus solitarius Nutrient Obesity Pathogenesis Pathway interactions Patients Pattern Peptides Perception Peripheral Pharmacological Treatment Phase Phosphorylation Physiological Plasma Play Population Prevention Process Prosencephalon Public Health Rattus Receptor Activation Receptor Gene Regulation Reporting Research Rodent Role Satiation Satiety Response Signal Transduction Site Small Intestines Stomach Structure of area postrema Structure of nucleus infundibularis hypothalami Suggestion Techniques Testing Time Study Treatment Efficacy Vagus nerve structure Ventricular Weight Gain Work base behavioral pharmacology cholecystokinin 9 common treatment dorsal motor nucleus energy balance exenatide feeding gastrointestinal gene therapy glucagon-like peptide hindbrain improved insight leptin receptor neural circuit neuromechanism neuroregulation prevent receptor receptor expression relating to nervous system research study response

项目摘要

Obesity and related metabolic disorders have become a tremendous public health problem. This proposal Investigates the neural circuitry that Integrates input from the adiposity hormone leptin and the gut-derived satiety signals cholecystokinin (CCK) and glucagon-like peptlde-1 (GLP-1), and the physiological relevance ofthe interactions between these signals for the control of food Intake and body weight. Available data support the hypothesis that the adiposity hormone leptin reduces food Intake in part by enhancing satiety responses to gastrointestinal signals, Includingj CCK. We have recently determined that leptin Interacts In a sirnilar rrianrier with GLP-1, but our data suggest that the leptin-CCK and leptin-GLP-1 interactions are mediated through different neuronal pathways, Here, we propose to Identify and compare brain areas In which leptin detection Is sufficient to enhance the responses to GLP-1 and CCK, using site-speclfic microinjections and gene therapy In normal rats and rats that lack leptin receptors due to genetic mutation. Next, we will Investigate whether leptin reduces food Intake and enhances the satiety response to gastrointestinal nutrients in part by modulating rats' sensitivity to endogenously released GLP-1 or CCK. Finally, we will determine whether altered sensitivity to GLP-i or CCK plays a role in the pathogenesis of diet-Induced obesity when rats are maintained on a high-fat diet, which produces leptin resistance, together, these studies will help to clarify how changes In body fat stores lead to compensatory adjustments in meal size, as well as how defects In this process may lead to obesity and metabolic disorders, and thus have the potential to significantly advance our understanding ofthe neural control of feeding and body weight.

肥胖及相关代谢紊乱已成为一个巨大的公共卫生问题。本研究旨在研究整合肥胖激素瘦素和肠源性饱腹感信号胆囊收缩素（CCK）和胰高血糖素样肽-1 （GLP-1）输入的神经回路，以及这些信号之间相互作用与控制食物摄入和体重的生理相关性。现有数据支持肥胖激素瘦素减少食物摄入的假设，部分是通过增强对胃肠道信号的饱腹反应，包括CCK。我们最近确定瘦素在类似的河流中与GLP-1相互作用，但我们的数据表明，瘦素-CCK和瘦素-GLP-1相互作用是通过不同的神经通路介导的。在这里，我们建议在正常大鼠和由于基因突变而缺乏瘦素受体的大鼠中，使用位点特异性微注射和基因治疗，确定并比较瘦素检测足以增强对GLP-1和CCK反应的大脑区域。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neural integration of satiation and food reward: role of GLP-1 and orexin pathways.

DOI：
10.1016/j.physbeh.2014.03.013
发表时间：
2014-09
期刊：
Physiology & behavior
影响因子：
2.9
作者：
Williams DL
通讯作者：
Williams DL

Expecting to eat: glucagon-like peptide-1 and the anticipation of meals.

期待进食：胰高血糖素样肽-1 和对进餐的期待。

DOI：
10.1210/en.2009-1372
发表时间：
2010
期刊：
Endocrinology
影响因子：
4.8
作者：
Williams,DianaL
通讯作者：
Williams,DianaL

Glucagon-like peptide 1 receptors in nucleus accumbens affect food intake.

DOI：
10.1523/jneurosci.3262-11.2011
发表时间：
2011-10-12
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Dossat AM;Lilly N;Kay K;Williams DL
通讯作者：
Williams DL

Hindbrain orexin 1 receptors influence palatable food intake, operant responding for food, and food-conditioned place preference in rats.