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FGF21-dependent mechanisms driving changes in energy expenditure during dietary protein restriction

FGF21 依赖性机制驱动饮食蛋白质限制期间能量消耗的变化

基本信息

批准号：
10359751
负责人：
Christopher D Morrison
金额：
$ 37万
依托单位：
LSU PENNINGTON BIOMEDICAL RESEARCH CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-15 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10359751
关键词：
Address Adipose tissue Animals Area Automobile Driving Biology Body Weight Brain Data Diet Dietary Proteins Endocrine Energy Metabolism Exhibits FGF21 gene Fatty acid glycerol esters Genetic Glucose Intolerance Goals Growth Health Hormones Hypothalamic structure Link Mediating Metabolic Metabolic hormone Metabolism Modeling Mus Neurons Non-Insulin-Dependent Diabetes Mellitus Obesity Pathway interactions Physiological Population Proteins Regulation Role Signal Transduction Signaling Protein Sympathetic Nervous System Testing Thermogenesis Transplantation Uncertainty Weight Gain Work base blood glucose regulation dietary restriction experimental study fibroblast growth factor 21 glucose tolerance improved nerve supply neural circuit neurobiological mechanism neuromechanism novel obesity treatment paraventricular nucleus physiologic model protein intake receptor relating to nervous system response

项目摘要

Project Summary Dietary protein intake alters energy expenditure and remodels adipose tissue, but the cellular mechanisms mediating these effects are largely undescribed. We recently discovered that the hormone FGF21 is robustly increased by dietary protein restriction and that mice lacking FGF21 fail to exhibit the expected changes in growth, energy expenditure or glucose homeostasis in response to dietary restriction. In addition, selective deletion of the FGF21 co-receptor beta-Klotho (Klb) from the brain also blocks the metabolic response to protein restriction. This discovery has redefined FGF21's physiological role by suggesting that it acts directly in the brain to coordinate the adaptive, homeostatic response to protein restriction. This project extends these data by 1) Identifying the FGF21-dependent neurobiological mechanisms that mediate changes in energy expenditure during protein restriction, and 2) Determining the mechanism through which protein restriction, via brain FGF21 signaling, remodels adipose tissue and thereby influences energy expenditure and metabolic health. This project will define the mechanism through which animals sense and respond to protein restriction while also delineating the mechanisms through which FGF21 acts in the brain to stimulate energy expenditure.

项目摘要膳食蛋白质摄入改变能量消耗和重塑脂肪组织，但细胞机制介导这些效应的机制在很大程度上未被描述。我们最近发现，激素FGF 21是强大的，增加，缺乏FGF 21的小鼠未能表现出预期的变化，生长、能量消耗或葡萄糖稳态。此外，选择性从脑中缺失FGF 21共受体β-Klotho（Klb）也阻断了对代谢的反应，蛋白质限制这一发现重新定义了FGF 21的生理作用，表明它直接作用于大脑来协调对蛋白质限制的适应性和自我平衡反应。该项目扩展了这些数据来源：1）确定介导能量变化的FGF 21依赖性神经生物学机制蛋白质限制期间的消耗，以及2）确定蛋白质限制通过的机制，通过脑FGF 21信号传导，重塑脂肪组织，从而影响能量消耗和代谢健康这个项目将定义动物感知和响应蛋白质限制的机制同时也描绘了FGF 21在大脑中刺激能量消耗的机制。