运动促进肝脏健康:表观遗传视域下非酒精性脂肪肝病的转归

Exercise Promotes Liver Health:The Regression of Non-alcoholic Fatty Liver Disease from an Epigenetic Perspective

非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)是与遗传或不良生活方式有关的代谢性疾病。表观遗传修饰的改变与NAFLD的发生发展密切相关。表观遗传修饰可被饮食和运动等环境因素影响。因此,本综述基于环境-基因范畴探讨表观遗传修饰在NAFLD发病机制中的作用,以及运动通过表观遗传修饰途径改善NAFLD的潜在机制。综述发现,运动可通过调控肝脏、骨骼肌等多器官/组织中的DNA甲基化修饰水平,直接或间接缓解肝脏脂肪变性;运动也可通过组蛋白修饰,调控肝脏糖脂代谢相关基因的表达,改善饮食诱导的肝脏糖脂代谢异常;运动还可通过调节微小RNA、长链非编码RNA等非编码RNA的表达,调控脂质合成分解、自噬和胰岛素信号传导等机制,进而改善NAFLD相关肝脏脂质沉积。重要的是,运动通过表观遗传修饰发挥的代谢益处具有明显的代际遗传效应,这为运动防治NAFLD提供了新的研究视角。

Non-alcoholic fatty liver disease(NAFLD)is a metabolic disease associated with genetics and unhealthy lifestyle.Changes in epigenetic modifications are closely related to the occurrence and development of NAFLD.Epigenetic modifications can be influenced by environmental factors such as diet and exercise.Therefore,based on the environmental-genetic category,this review investigated the role of epigenetic modifications in the pathogenesis of NAFLD and the potential mechanisms by which exercise improves NAFLD through epigenetic modifications pathway.It was found that exercise can directly or indirectly alleviate hepatic steatosis by regulating DNA methylation modification levels in multiple organs/tissues such as liver and skeletal muscle.Exercise can also regulate the expression of genes related to hepatic glucose and lipid metabolism through histone modifications,and improve diet-induced abnormalities in hepatic glucose and lipid metabolism.Additionally,exercise can regulate the expression of non-coding RNA,such as microRNA and long non-coding RNA.It can regulate the mechanisms of lipid synthesis and decomposition,autophagy,insulin signaling,and then improve hepatic lipid deposition related to NAFLD.Importantly,the metabolic benefits of exercise through epigenetic modifications demonstrated evident intergenerational genetic effects.This provided a novel research perspective for exercise in prevention and treatment of NAFLD.