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Neuronal Inputs of Body Fat Regulation

体脂肪调节的神经元输入

基本信息

批准号：
8352025
负责人：
Tania Reis
金额：
$ 12.73万
依托单位：
UNIVERSITY OF COLORADO DENVER
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：
2012-07-15 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8352025
关键词：
Ablation Address Adipocytes Adult Affect Animals Area Award Behavior Behavioral Binding Biochemical Biological Assay Body Weight Body fat Brain Brain Part Brain region Cells Complex Control Animal Couples Cytoskeleton Defect Diet Drosophila genus Drosophila melanogaster Energy Metabolism Epidemic Family Fatty Acids Fatty acid glycerol esters Fractionation Gene Expression Profile Genes Genetic Genetic Screening Genome Goals Homeostasis Hormones Human Individual Inherited Isotope Labeling Laboratories Learning Ligands Link Lipids Locomotion Mammals Maps Mediating Membrane Metabolic Metabolism Modeling Molecular Molecular Genetics Motor Activity Mutate National Institute of Diabetes and Digestive and Kidney Diseases National Research Service Awards Nervous System Physiology Nervous system structure Neuraxis Neurons Neuropeptides Nutrient Obesity Pathway interactions Phenotype Physical activity Physiology Play Population Predisposing Factor Proteins Proteome RNA Interference Receptor Signaling Regimen Regulation Regulatory Pathway Resistance Risk Factors Role Signal Transduction Signaling Molecule Starvation Susceptibility Gene Tissues Variant Work Yeasts addiction adiponectin base energy balance fly food consumption genetic analysis inhibitor/antagonist insight loss of function mutant novel obesity treatment overexpression prevent receptor research study response tool trend

项目摘要

DESCRIPTION (provided by applicant): An individual's genetic makeup remains a major predisposing factor to obesity, with recent trends in diet and behavior also contributing to the current obesity epidemic. Genetic background is responsible for about half of the variation in body weight within human populations, but we currently understand only a few of the pathways affected by hereditary risk factors. Importantly, the limited information we have about obesity-predisposing genes suggests that many are expressed primarily in the brain. Indeed, the central nervous system clearly plays important but poorly understood roles in maintaining organismal energy homeostasis. Experiments in this proposal will target neuronal roles in body fat regulation in the fruit fly Drosophila melanogaster. Drosophila is a powerful obesity model: flies have a complex physiology rivaling that of mammals, plus a streamlined genome in which a single gene often serves the function of multiple redundant mammalian genes. The goals of this project are to generate a neuronal map of body fat regulation by identifying regions of the brain whose functions are required to prevent excess body fat, and to determine the functions of two genes that were identified in an unbiased screen for fat mutants and which appear to operate in the brain. One of the new fat genes is an uncharacterized receptor related to those that bind adiponectin, a mammalian protein secreted from fat cells that controls food consumption and fat storage. Identifying the molecule bound by the fly receptor may reveal a new pathway by which the brain communicates with other tissues to prevent obesity. The other gene has been implicated in both learning-related behaviors like addiction and, most importantly, the regulation of locomotor activity in response to nutrient availability. Thus, this factor may represent an otherwise elusive opportunity to dissect the relationship between physical activity and energy storage. These studies will provide new insights into the neuronal components of human obesity, and identify new potential targets for its treatment. PUBLIC HEALTH RELEVANCE: The central nervous system - in particular, the brain - appears to play critical roles in organismal energy homeostasis, but the pathways involved are poorly characterized. This work will pinpoint regions of the Drosophila brain required to prevent excess body fat, and uncover new pathways by which the brain coordinates the functions of other tissues for this purpose, generating targets for new human obesity treatments.

描述（由申请人提供）：个人的基因构成仍然是肥胖的主要诱发因素，最近的饮食和行为趋势也导致了当前的肥胖流行。人类体重变化的一半左右是由遗传背景造成的，但我们目前只了解受遗传风险因素影响的少数途径。重要的是，我们掌握的有关肥胖易感基因的有限信息表明，许多基因主要在大脑中表达。事实上，中枢神经系统在维持机体能量稳态方面显然发挥着重要但人们知之甚少的作用。该提案中的实验将针对果蝇体内脂肪调节中的神经元作用。果蝇是一种强大的肥胖模型：果蝇具有与哺乳动物相媲美的复杂生理机能，加上精简的基因组，其中单个基因通常充当多个冗余哺乳动物基因的功能。该项目的目标是通过识别防止身体脂肪过多所需的功能的大脑区域来生成身体脂肪调节的神经元图，并确定在脂肪突变体的无偏筛选中鉴定出的两个基因的功能，这两个基因似乎在大脑中起作用。其中一个新的脂肪基因是一种未表征的受体，与结合脂联素的受体相关，脂联素是一种从脂肪细胞分泌的哺乳动物蛋白质，控制食物消耗和脂肪储存。识别果蝇受体结合的分子可能会揭示大脑与其他组织沟通以预防肥胖的新途径。另一个基因与成瘾等与学习相关的行为有关，最重要的是，与营养可用性的反应调节运动活动有关。因此，这个因素可能代表着一个难以捉摸的机会来剖析身体活动和能量储存之间的关系。这些研究将为人类肥胖的神经元组成提供新的见解，并确定其治疗的新的潜在靶标。公共健康相关性：中枢神经系统，特别是大脑，似乎在有机体能量稳态中发挥着关键作用，但所涉及的途径却知之甚少。这项工作将查明果蝇大脑中防止身体脂肪过多所需的区域，并揭示大脑为此目的协调其他组织功能的新途径，从而为新的人类肥胖治疗产生目标。