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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：
7300935
负责人：
Diana L Williams
金额：
$ 7.99万
依托单位：
UNIVERSITY OF WASHINGTON
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 2008-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7300935
关键词：
Accounting Address Adipose tissue Affect Afferent Pathways Agonist Animals Anorexia Appendix 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 DVC 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 GLP-I receptor Gastrointestinal tract structure Gene Mutation Genetic 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 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 Principal Investigator Process Prosencephalon Public Health Rattus Receptor Activation Receptor Gene Regulation Reporting Research Research Personnel 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 dorsal motor nucleus energy balance exenatide feeding gastrointestinal gene therapy glucagon-like peptide 1 hindbrain improved insight leptin receptor neural circuit neural model neuromechanism neuroregulation prevent programs receptor receptor expression relating to nervous system research study response size

项目摘要

DESCRIPTION (provided by applicant): 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 peptide-1 (GLP-1), and the physiological relevance of the 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, including CCK. We have recently determined that leptin interacts in a similar manner 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-specific 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-1 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 of the neural control of feeding and body weight. Lay Description: This research focuses on how the brain detects stored energy in fat along with the presence of nutrients in the gut, and then integrates that information to determine how much food to eat. Specifically, we will examine the brain areas that mediate these effects, as well as the relevance of these interactions to normal control of feeding and the development of obesity. Our studies will improve our understanding of the neural circuitry that regulates food intake and body weight, and will help identify biological factors that contribute to the development and maintenance of obesity.

描述（由申请人提供）：