Central FGF21-mediated control of energy expenditure.

项目总结/文摘

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.