Irisin调节肝脏内质网应激改善肝内脂质沉积的作用及机制研究

Nonalcoholic fatty liver disease (NAFLD) has become a new challenge in the field of contemporary medicine. Endoplasmic reticulum stress (ERS) plays an important role in its pathogenesis. At present, NAFLD has no recognized drugs, changing life-style is still a first-line treatment. We found that exercise significantly reduced intrahepatic triglyceride (IHTG) content. Irisin is a newly found myokine, which is closely related to obesity-related metabolic disorders. We found that IHTG contents in NAFLD patients were negatively correlated with serum irisin levels, and exercise was able to increase irisin levels，but whether irisin is causative is not determined yet. Therefore, we speculate that the mechanism of exercise to improve NAFLD may be that the increased expression of irisin induced by exercise reduces ERS, and then reduces intrahepatic lipid synthesis to improve hepatic lipid deposition. On the basis of the above important findings, we will carry out the following research:1.Whether irisin could regulate the hepatic triglyceride metabolism? 2.The downstream signaling pathway of irisin: the role and mechanism of irisin on liver ERS. This study not only helps elucidate the regulation of irisin on hepatic triglyceride metabolism, but also provides new clues for revealing the pathophysiological processes of NAFLD and even screening new drug targets.

非酒精性脂肪肝病（NAFLD）已成为当代医学领域的新挑战，内质网应激（ERS）在其发病机制中扮演重要作用，目前NAFLD尚无公认的防治药物，改变生活方式仍是一线治疗方案。我们发现运动可降低肝脏甘油三酯（IHTG）含量。Irisin是近年来发现的肌细胞因子，其与代谢紊乱有密切关系。我们发现NAFLD患者IHTG含量和血清Irisin负相关，且运动能提高Irisin，但Irisin与NAFLD因果关系尚未确定。我们推测运动改善NAFLD的可能机制是运动使Irisin表达增加，减轻ERS，从而使肝内脂质合成减少来改善肝内脂质沉积。本项目将在上述发现的基础上研究：1.Irisin是否能够调控肝内甘油三酯代谢；2.Irisin下游信号通路：Irisin对肝脏ERS作用及机制。这一研究不仅有助于阐明Irisin对肝脏脂质代谢的调控作用，也可为揭示NAFLD的病理生理过程，乃至药物靶点的筛选提供新线索。