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.

项目概要/摘要 生存需要摄入膳食蛋白质或必需氨基酸，现有证据 表明身体能够感知蛋白质摄入量的减少并做出适应性反应。这 莫里森实验室此前表明，对蛋白质限制的适应性代谢反应是 依赖于大脑中通过其辅助受体 beta-klotho (Klb) 进行的 FGF21 信号传导，使得 饮食蛋白质限制增加能量消耗、上调产热基因的能力 在白色和棕色脂肪组织（WAT 和 BAT）中表达，并改善血糖 体内平衡完全依赖于 FGF21 介导的肝脏到大脑的信号。目标 该 F32 项目的目标是： 1) 识别 FGF21 反应性神经元群体并对其进行表型分析 介导蛋白质限制期间能量消耗的增加，以及 2) 确定 是否需要下游的 FGF21 依赖性脂肪组织重塑 蛋白质限制期间代谢终点的变化。了解具体情况 CNS 中的 FGF21 信号将通过该机制识别新的神经回路 调节能量消耗和脂肪组织代谢，这样做可能会导致 针对难以保持健康体重的个体减少肥胖的新干预措施。