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Interactions of Leptin and the Melanocortin System

瘦素和黑皮质素系统的相互作用

基本信息

批准号：
9768441
负责人：
JOEL K. ELMQUIST
金额：
$ 41.81万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9768441
关键词：
ADRA2A gene Acute Adipocytes Adipose tissue Adrenergic Receptor Adult Automobile Driving Behavioral Blood Body Weight Body fat Brain Complex Cues Data Development Diabetes Mellitus Disease Eating Endocrine Energy Metabolism Exposure to Fasting Fatty acid glycerol esters Food Energy Functional disorder Genetically Engineered Mouse Glucose Hand Hepatic Homeostasis Hypothalamic structure Impairment Incidence Insulin Insulin Resistance Leptin Lipids Liver Mediating Metabolic Metabolism Modeling Molecular Mus Nervous system structure Neuraxis Neurons Neurosecretory Systems Nutritional status Obesity Pathway interactions Play Pro-Opiomelanocortin Process Production Regulation Role Signal Transduction Surface Sympathetic Nervous System System Testing Tissues Visceral base blood glucose regulation designer receptors exclusively activated by designer drugs diabetes mellitus therapy energy balance falls fatty acid oxidation feeding genetic manipulation glucose metabolism glucose production insulin sensitivity leptin receptor lipid biosynthesis liver development liver function mouse model prenatal receptor targeted treatment

项目摘要

Abstract The increasing rates of obesity and diabetes highlight the need to understand the brain circuits and cellular mechanisms regulating energy balance and glucose homeostasis. Prominent among these is the central leptin- melanocortin system, which includes the pro-opiomelanocortin (POMC) neurons, subsets of which express leptin receptors (LEPRs). Understanding how leptin differentially regulates energy balance versus glucose homeostasis is key for the development of anti-obesity and anti-diabetes therapies. Early observations based on prenatal genetic manipulations led to the widely-held model that LEPR-expressing POMC neurons mediated the metabolic actions of leptin, however, evidence now suggests that these pathways are more complex than originally anticipated. The current application extends our early developmental models by directly testing the role of leptin action in adult melanocortin neurons in regulating glucose metabolism and responding to dynamic challenges, including fasting and cold exposure. We also have in hand a model in which liver insulin resistance can be induced in a temporal manner, allowing us to investigate the role of the leptin- melanocortin pathway in its development. These studies will broaden our understanding of the functional mechanism by which the leptin-melanocortin system regulates endocrine, autonomic, and behavioral functions, particularly at the level of adipose tissues and liver.

摘要