Myokine Control of Hepatic Steatosis

肌因子对肝脂肪变性的控制

基本信息

批准号：
9181162
负责人：
KENNETH WALSH
金额：
$ 24.68万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
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：
2016-09-15 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9181162
关键词：
ADD-1 protein Adenoviruses Adult Aerobic Affect Aging Attenuated Behavior Therapy Biogenesis Body Weight Body fat Cardiovascular Diseases Cardiovascular Physiology Complication Data Development Diabetes Mellitus Diet Disease Dominant-Negative Mutation Endocrine Event Fatty Liver Fatty acid glycerol esters Follistatin Freezing Gene Expression Glucose tolerance test Growth Heart Diseases Heavy Drinking Hepatic Hepatocyte Human Individual Inflammation Insulin Resistance Lipids Liver Liver diseases Mediating Medical Metabolic Metabolic syndrome Metabolism Mitochondria Molecular Mus Muscle Non-Insulin-Dependent Diabetes Mellitus Obese Mice Obesity Pharmaceutical Preparations Physical Exercise Physical activity Play Population Process Proteins Recombinants Resistance Reverse Transcriptase Polymerase Chain Reaction Risk Role Sampling Signal Transduction Skeletal Muscle Sucrose Testing Therapeutic Tissues Training Triglycerides Weight autocrine base blood glucose regulation chronic liver disease diet and exercise feeding histological stains human study insulin tolerance liver metabolism mouse model muscle form non-alcoholic fatty liver nonalcoholic steatohepatitis overexpression paracrine prevent protective effect skeletal muscle wasting strength training transcription factor

项目摘要

SUMMARY Non-alcoholic fatty liver disease (NAFLD) is a liver condition characterized by hepatic fat accumulation (hepatic steatosis) in the absence of excessive alcohol consumption. This disorder represents the most common form of chronic liver disease and is associated with obesity, aging and diabetes. An increasing body of evidence suggests a strong connection between reduced skeletal muscle mass/function and NAFLD, but the underlying mechanisms remain unknown. It has been suggested that skeletal muscle mediates some of the systemic benefits of physical exercise through the secretion of multiple bioactive proteins called myokines. Follistatin- like-1 (Fstl1) is an emerging myokine that is upregulated in a mouse model that mimics strength training- induced muscle growth, and has been shown to be upregulated in humans by either aerobic or strength training. Nothing is known about the potential metabolic actions of this myokine. The present project will test the hypothesis that skeletal muscle-derived Fstl1 exerts protective metabolic actions in the liver, preventing obesity-induced hepatic lipid accumulation and associated insulin resistance. This project has two specific aims: 1. To examine the effects of skeletal muscle-derived Fstl1 in the development of hepatic steatosis and insulin resistance in obese mice; 2. To investigate the role of AMPK signaling in the protective effects of Fstl1 against hepatic steatosis

概括非酒精性脂肪性肝病（NAFLD）是一种以肝脏脂肪堆积（肝脂肪堆积）为特征的肝脏疾病。脂肪变性）在没有过量饮酒的情况下。这种疾病是最常见的形式慢性肝病与肥胖、衰老和糖尿病有关。越来越多的证据表明骨骼肌质量/功能减少与 NAFLD 之间存在密切联系，但潜在的机制仍不清楚。有人认为骨骼肌介导一些全身性的体育锻炼的好处是通过分泌多种称为肌因子的生物活性蛋白质来实现的。卵泡抑素- like-1 (Fstl1) 是一种新兴的肌因子，在模拟力量训练的小鼠模型中上调 - 诱导肌肉生长，并且已被证明可以通过有氧运动或力量在人类中上调训练。关于这种肌因子的潜在代谢作用尚不清楚。本项目将测试假设骨骼肌来源的 Fstl1 在肝脏中发挥保护性代谢作用，防止肥胖引起的肝脏脂质积累和相关的胰岛素抵抗。这个项目有两个具体的目的： 1. 研究骨骼肌来源的 Fstl1 在肝脂肪变性发展中的作用和肥胖小鼠的胰岛素抵抗； 2. 探讨AMPK信号在Fstl1保护作用中的作用对抗肝脂肪变性