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FGF21 is an endocrine signal of protein restriction

FGF21是蛋白质限制的内分泌信号

基本信息

批准号：
9388340
负责人：
Christopher D Morrison
金额：
$ 33.3万
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：
2015
资助国家：
美国
起止时间：
2015-12-01 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9388340
关键词：
Acute Adipose tissue Amino Acids Attention Attenuated Automobile Driving Biological Body Weight Clinical Data Detection Diabetes Mellitus Diet Dietary Proteins Eating Endocrine Energy Metabolism Eukaryotic Initiation Factor-2 FGF21 gene Fasting Genetic Models Glucose Glucose Intolerance Growth Health Hepatic Hormones Human In Vitro Link Longevity Macronutrients Nutrition Mediating Mediator of activation protein Metabolic Metabolic hormone Metabolism Molecular Mus Nutrient Obesity PPAR alpha Pathway interactions Pharmacology Phosphorylation Phosphotransferases Physiological Protein-Restricted Diet Proteins Publishing Regulation Regulatory Pathway Reporting Rodent Role Signal Transduction Signaling Protein Site Testing Thermogenesis Work behavioral response comparative detector dietary restriction energy balance improved insulin sensitivity ketogenic diet knock-down link protein mRNA Expression novel protein intake protein metabolism public health relevance response virtual

项目摘要

DESCRIPTION (provided by applicant): The restriction of dietary protein intake induces adaptive changes in metabolism and increases lifespan, but the cellular mechanisms mediating the detection of dietary protein restriction and its effects on health and longevity are virtually undescribed. We recently discovered that the hormone FGF21 is robustly induced by dietary protein restriction, and that mice lacking FGF21 fail to alter food intake, energy expenditure or body weight in response to dietary protein restriction. These data not only redefine the physiological role for FGF21, they also identify a fundamentally novel endocrine mechanism that appears to explain the metabolic effects of protein restriction. This project extends these data by 1) Identifying the cellular mechanism whereby dietary protein restriction increases hepatic FGF21, 2) Determining whether FGF21 signaling within the CNS or adipose tissue is required for the effects of dietary protein restriction on energy expenditure, and 3) Delineating the mechanisms through which protein restriction protects against HFD-induced obesity and glucose intolerance. This project will redefine the physiological role of FGF21 in the adaptive responses to nutrient restriction and provide a novel mechanistic explanation for the relationship between dietary protein, metabolism and health.

描述（由申请人提供）：限制膳食蛋白质摄入会诱导代谢的适应性变化并延长寿命，但介导膳食蛋白质限制检测的细胞机制及其对健康和寿命的影响几乎没有描述。我们最近发现，激素FGF21是由饮食蛋白质限制强烈诱导的，缺乏FGF21的小鼠不能改变食物摄入量，能量消耗或体重以响应饮食蛋白质限制。这些数据不仅重新定义了FGF21的生理作用，还确定了一种全新的内分泌机制，似乎可以解释蛋白质限制的代谢效应。该项目通过以下方式扩展了这些数据： 1)确定膳食蛋白质限制增加肝FGF 21的细胞机制，2）确定CNS或脂肪组织内的FGF 21信号传导是否是膳食蛋白质限制对能量消耗的影响所必需的，和3）描述蛋白质限制保护免受HFD诱导的肥胖和葡萄糖耐受不良的机制。该项目将重新定义FGF21在营养限制适应性反应中的生理作用，并为膳食蛋白质，代谢和健康之间的关系提供新的机制解释。