Central FGF21-mediated control of energy expenditure.

项目总结/摘要 膳食蛋白质或必需氨基酸摄入是生存所必需的，现有证据表明 表明身体感觉到并适应性地对蛋白质摄入量的减少做出反应。的 莫里森实验室先前已经证明，对蛋白质限制的适应性代谢反应是 依赖于脑中FGF 21通过其共受体β-klotho（Klb）的信号传导，使得 限制蛋白质摄入增加能量消耗，上调产热基因 在白色和棕色脂肪组织（WAT和BAT）中表达，并改善葡萄糖 体内平衡完全依赖于这种FGF 21介导的肝到脑信号。的目标 本F32项目的主要目的是：1）鉴定FGF 21反应性神经元的表型群体 在蛋白质限制期间介导能量消耗的增加，以及2）确定 是否需要下游的，FGF 21依赖性的脂肪组织重塑， 蛋白质限制期间代谢终点的变化。了解具体 通过这种机制，CNS中的FGF 21信号将识别新的神经回路， 调节能量消耗和脂肪组织代谢，这样做可能导致 新的干预措施，以减少那些努力保持健康体重的人的肥胖。

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.