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Mechanisms of metabolic, inflammatory and healthspan enhancement by 17a-estradiol

17a-雌二醇增强代谢、炎症和健康寿命的机制

基本信息

批准号：
9336760
负责人：
Michael B Stout
金额：
$ 13.88万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9336760
关键词：
5&apos -AMP-activated protein kinase Address Adipose tissue Aerobic Exercise Aging Aging-Related Process Animals Applications Grants Area Binding Bioinformatics Biological Assay Biological Models Body Weight decreased Ca(2+)-Calmodulin Dependent Protein Kinase Calcium/calmodulin-dependent protein kinase Caloric Restriction Cardiovascular system Cell Culture Techniques Chronic Chronic Disease Collaborations Development Diabetes Mellitus Disease Drug or chemical Tissue Distribution Elderly Estradiol Estrogen Receptors Exposure to FRAP1 gene Faculty Flow Cytometry Functional disorder Funding Future Goals Homeostasis Hormones Human Immunofluorescence Immunologic Immunohistochemistry Inflammation Inflammatory Insulin Interleukin-1 beta Intervention Knock-out Knockout Mice Knowledge Lead Ligand Binding Ligands Link Lipids Longevity MAP3K7 gene Macronutrients Nutrition Metabolic Metabolic Diseases Metabolism Metformin Mitochondria Molecular Mus NADH NF-kappa B Obesity Pathway interactions Pharmacology Phenotype Phosphotransferases Protein Kinase Proteins Proteomics Recombinant Proteins Recruitment Activity Research Research Activity Research Personnel Resveratrol Risk Factors Rodent SIRT1 gene STK11 gene Secure Sepharose Signal Transduction Sirolimus Small Interfering RNA Sorting - Cell Movement Supervision System TNF gene Technical Expertise Techniques Testing Time Tissues Training Transforming Growth Factors Visceral Western Blotting Woman Work age related aged career development design detection of nutrient enantiomer follow-up laboratory experience macrophage male member men novel overexpression receptor research and development young adult

项目摘要

PROJECT SUMMARY/ABSTRACT The research and career development activities outlined in this application have been designed to equip the candidate, Dr. Michael Stout, with the scientific and technical expertise necessary to become an independent investigator. The proposed research aims to elucidate the mechanisms responsible for the alleviation of age- related metabolic and inflammatory dysfunction by 17α-estradiol and identify the receptor(s)/pathway(s) by which these effects occur. As such, the candidate will receive additional training in signaling networks directly relevant to this area of research through intensive coursework and hands-on laboratory experience under the supervision of Drs. James Kirkland, Eduardo Chini, and Sundeep Khosla. The short-term objectives of this application are to enhance the candidate's knowledge of nutrient-sensing and inflammatory pathway interactions and develop technical skills to evaluate these relationships in culture- and animal-model systems. The long-term goals of this application are to enable the candidate, as a newly-hired faculty member, to secure protected time for research activities, establish new collaborations, and develop a novel line of research that produces competitive grant proposals for future funding. Preliminary studies performed by the candidate under the direction of Dr. James Kirkland indicate that 17α-estradiol enhances metabolic function and alleviates inflammation in older mice through pathways that are central to metabolic homeostasis and the aging process. This proposal will expand upon these findings by unraveling the intracellular mechanisms responsible for these phenotypes while also identifying receptor(s)/pathway(s) by which 17α-estradiol elicits these downstream effects. The overall hypothesis is that 17α-estradiol signals through an uncharacterized receptor/pathway leading to activation of AMPK and alleviation of metabolic and inflammatory dysfunction. The candidate will test this hypothesis through the following aims: 1) Determine if metabolic enhancement by 17α-estradiol is AMPK-dependent; 2) Determine if 17α-estradiol reduces inflammation by suppressing mTOR and/or NFKB; and 3) Identify the receptor(s)/pathway(s) by which 17α-estradiol elicits its cellular effects. This work will significantly enhance the understanding of molecular and cellular pathways by which 17α-estradiol elicits its effects which could lead to the development of novel treatments for aging- and/or obesity-related metabolic and inflammatory disorders.

项目总结/文摘