Central FGF21-mediated control of energy expenditure.

FGF21 介导的中枢能量消耗控制。

• 批准号: 10387852
• 负责人: REDIN A SPANN
• 金额: $ 7.05万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-25 至 2023-09-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10387852
• 关键词: Adipocytes; Adipose tissue; Appetitive Behavior; Area; Brain; Brown Fat; Cardiovascular Diseases; Data; Diabetes Mellitus; Dietary Proteins; Energy Metabolism; Essential Amino Acids; Gene Expression; Genetic; Genetic Transcription; Goals; Health; Hypothalamic structure; Immunohistochemistry; Individual; Intake; Intervention; Lead; Liver; Measures; Mediating; Metabolic; Metabolic hormone; Metabolism; Methods; Mus; Neuraxis; Neurons; Neurotransmitter Receptor; Nucleus solitarius; Obesity; Operative Surgical Procedures; Output; Pathway interactions; Phenotype; Physiological; Population; Protein-Restricted Diet; Proteins; Reporter; Signal Transduction; Sympathetic Nervous System; Testing; Viral; Work; blood glucose regulation; body sense; comorbidity; effective therapy; fibroblast growth factor 21; healthy weight; hormonal signals; improved; neural circuit; novel; protein intake; receptor; recombinase; response; single-cell RNA sequencing

PROJECT SUMMARY/ABSTRACT Dietary protein or essential amino acid intake is required for survival, and available evidence suggests that the body senses and adaptively responds to reductions in protein intake. The Morrison Lab has previously shown that adaptive metabolic responses to protein restriction are dependent on FGF21 signaling in the brain via its co-receptor beta-klotho (Klb), such that the ability of dietary protein restriction to increase energy expenditure, upregulate thermogenic gene expression in white and brown adipose tissue (WAT and BAT), and improve glucose homeostasis is completely dependent on this FGF21-mediated liver to brain signal. The goals of this F32 project are to: 1) Identify and phenotype populations of FGF21-responsive neurons that mediate increases in energy expenditure during protein restriction, and 2) determine whether the downstream, FGF21-dependent remodeling of adipose tissue is required for changes in metabolic endpoints during protein restriction. Understanding the specific mechanism through which FGF21 signals in the CNS will identify novel neural circuits that regulate energy expenditure and adipose tissue metabolism, and in so doing potentially lead to new interventions to decrease adiposity in individuals who struggle to maintain a healthy weight.

项目摘要/摘要 生存需要饮食蛋白或必需氨基酸摄入量 表明身体会感觉和适应地响应蛋白质摄入的减少。这 Morrison Lab先前已经表明，对蛋白质限制的自适应代谢反应是 取决于大脑中的FGF21信号传导通过其共受体β-klotho（KLB），因此 饮食蛋白限制增加能量消耗的能力，上调热基因 在白色和棕色脂肪组织（WAT和BAT）中的表达，并改善葡萄糖 稳态完全取决于FGF21介导的肝脏的肝脏信号。目标 该F32项目是：1）识别FGF21响应神经元的识别和表型种群 介导蛋白质限制期间能量消耗的增加，2）确定 下游是否需要脂肪组织的FGF21依赖性重塑 蛋白质限制期间代谢终点的变化。了解具体 中枢神经系统中FGF21信号将确定新型神经回路的机制 调节能量消耗和脂肪组织代谢，并因此可能导致 新的干预措施以减少难以维持健康体重的人的肥胖。