Myokine Control of Hepatic Steatosis

总结 非酒精性脂肪性肝病（NAFLD）是一种以肝脂肪积聚（肝硬化）为特征的肝脏病症。 脂肪变性）在没有过量饮酒的情况下。这种疾病是最常见的 它是慢性肝病的一种表现形式，与肥胖、衰老和糖尿病有关。越来越多的证据 提示骨骼肌质量/功能降低与NAFLD之间存在密切联系，但潜在的 机制仍然未知。已经表明，骨骼肌介导了一些全身性的 身体锻炼的好处通过分泌多种生物活性蛋白质称为myokines。卵泡抑素- Like-1（Fstl 1）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，并已被证明是上调在人类无论是有氧或力量 训练关于这种肌因子的潜在代谢作用还不清楚。本项目将测试 骨骼肌来源的Fstl 1在肝脏中发挥保护性代谢作用， 肥胖诱导的肝脏脂质蓄积和相关的胰岛素抵抗。该项目有两个具体的 目标：1.研究骨骼肌源性Fstl 1在肝脂肪变性发展中的作用， 肥胖小鼠的胰岛素抵抗; 2.研究AMPK信号通路在Fstl 1保护作用中的作用， 抗肝脂肪变性

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