Neuronal Inputs of Body Fat Regulation

体脂肪调节的神经元输入

• 批准号: 8662259
• 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
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8662259
• 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

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.

描述（由申请人提供）：个体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。遗传背景对人类体重变化的影响约占一半，但我们目前只了解少数受遗传风险因素影响的途径。重要的是，我们对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。的确，中枢神经系统在维持机体能量平衡方面扮演着重要的角色，但人们对其知之甚少。本实验将针对黑腹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，加上流线型基因组，其中单个基因通常具有多个冗余哺乳动物基因的功能。该项目的目标是通过识别大脑中需要防止过量体脂的区域来生成体脂调节的神经元图，并确定在脂肪突变体的无偏筛选中发现的两个基因的功能，这两个基因似乎在大脑中起作用。其中一种新的脂肪基因是一种与脂联素结合的受体相关的未知受体，脂联素是一种由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。识别苍蝇受体结合的分子可能会揭示大脑与其他组织沟通以防止肥胖的新途径。另一个基因与学习相关的行为，如成瘾，最重要的是，对运动活动的调节，以响应营养的可用性都有关系。因此，这个因素可能代表了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成分提供新的见解，并确定其治疗的新潜在靶点。

项目成果

Coordination between Drosophila Arc1 and a specific population of brain neurons regulates organismal fat.

果蝇 Arc1 和特定脑神经元群之间的协调调节有机体脂肪。

• DOI: 10.1016/j.ydbio.2015.07.021
• 发表时间: 2015
• 期刊: Developmental biology
• 影响因子: 2.7
• 作者: Mosher,Jeremy;Zhang,Wei;Blumhagen,RachelZ;D'Alessandro,Angelo;Nemkov,Travis;Hansen,KirkC;Hesselberth,JayR;Reis,Tânia
• 通讯作者: Reis,Tânia