Central FGF21-mediated control of energy expenditure.

项目摘要/摘要 饮食中的蛋白质或必需氨基酸的摄入量是生存所必需的，并且有证据表明 表明身体对蛋白质摄入量的减少有感知和适应性反应。这个 莫里森实验室此前已经表明，对蛋白质限制的适应性代谢反应是 依赖于大脑中的FGF21信号，通过其辅助受体β-klotho(KLb)，从而使 限制饮食蛋白质增加能量消耗，上调生热基因的能力 在白色和棕色脂肪组织(Wat和BAT)中表达，并改善血糖 动态平衡完全依赖于这种FGF21介导的肝到脑信号。目标 这个F32项目的目的是：1)鉴定FGF21反应神经元的群体和表型 在蛋白质限制期间调节能量消耗增加，以及2)确定 是否需要下游依赖于FGF21的脂肪组织重塑 蛋白质限制期间代谢终点的变化。了解具体情况 中枢神经系统中FGF21信号识别新的神经回路的机制 调节能量消耗和脂肪组织代谢，这样做可能会导致 在努力保持健康体重的个人中减少肥胖的新干预措施。

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.