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Benefits of dietary essential amino acid restriction

限制膳食必需氨基酸的好处

基本信息

批准号：
8386640
负责人：
JAMES R. MITCHELL
金额：
$ 35.07万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-12-01 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8386640
关键词：
Acetaminophen Amino Acids Anabolism Animals Antioxidants Binding Blood Body Weight Body Weight decreased Branched-Chain Amino Acids Clinic DNA Methylation Data Diet Eating Essential Amino Acids Gene Expression Genes Glutathione Goals Health Individual Kidney Knockout Mice Laboratory Organism Leucine Literature Liver Longevity Malnutrition Mammals Measures Metabolic Metabolic Diseases Metabolism Methionine Molecular Mus Mutant Strains Mice Nutrient Organ Oxidative Stress Pathology Pathway interactions Phenotype Phosphotransferases Physiology Proteins Regimen Reperfusion Injury Resistance Response Elements Rodent Role Serum Signal Transduction Signal Transduction Pathway Stress TSC1 gene Testing Time Tissues Toxic effect Translating Translational Derepression Tryptophan Up-Regulation Work activating transcription factor acute stress blood glucose regulation deprivation detection of nutrient dietary restriction improved inhibitor/antagonist insight insulin sensitivity mouse model public health relevance renal ischemia transcription factor

项目摘要

DESCRIPTION (provided by applicant): Dietary restriction (DR), or reduced food intake without malnutrition, is highly beneficial in a variety of experimental organisms using a number of endpoints, including glucose homeostasis, acute stress resistance and longevity. While energy restriction is commonly thought to the key to a successful DR regimen, a small but growing body of literature points to the dominant role of nutrient restriction. Long-term restriction of dietary methionine, an essential amino acid, results in increased lifespan, health span and acute stress resistance in experimental rodents. Although the phenotype resembles that of DR, it occurs in the absence of energy restriction. The benefits of methionine restriction are thought to involve perturbation of one or more methionine-requiring pathways, such as DNA methylation or glutathione biosynthesis. Our preliminary data indicate that short-term restriction of dietary methionine improves glucose homeostasis and stress resistance within as little as six days. Importantly, we have also found that restriction of two other essential amino acids - tryptophan and leucine - lend similar benefits. We hypothesize that restriction of any essential amino acid will rapidly trigger changes in animal physiology resulting in improved glucose homeostasis and increased stress resistance. Our aim is to elucidate relevant upstream amino acid sensing pathways and downstream effectors of oxidative stress resistance with the ultimate goal of translating these benefits to the clinic.

描述（由申请人提供）：