表观遗传学与非酒精性脂肪肝及相关代谢紊乱

Epigenetics in the pathogenesis of nonalcoholic fatty liver disease and the related metabolic disorders

随着生活方式的改变，非酒精性脂肪肝（NAFLD）的发生率逐渐升高，且肝脏脂肪异位沉积会引起胰岛素抵抗，进而促进2型糖尿病的发生，其发病机制目前尚不明确。表观遗传学受环境、饮食等因素的影响，对基因表达具有调控作用。研究表明，细胞色素C亚单位7A多肽1（COXTA1）、过氧化物酶体增殖物活化受体γ共激活因子-1α（PGC-1α）及烟酰胺腺嘌呤二核苷酸脱氢酶（NDUFB）6和葡萄糖激酶启动子CpG位点的高度甲基化可导致相应基因的表达水平下降，而这些基因的表达量下调与胰岛素抵抗的发生密切相关。同时研究报道在NAFLD存在多种microRNA异常表达，因此基因的表观遗传修饰如DNA甲基化、组蛋白修饰及microRNA在NAFLD及糖脂代谢异常的发生机制中起重要作用。

Nonalcoholic fatty liver disease （NAFLD） is an increasingly recognized clinical syndrome,which is tightly associated with hepatic insulin resistance and type 2 diabetes. The pathogenesis of NAFLD and the related metabolic disorders remains unclear. Gene levels are regulated by epigenetic modification,which is affected by environmental factors and different diets. Promoters of COX7A1, PGC-1a and NDUFB6,indicated by previous studies, are hypermethylated in skeletal muscle or islet from patients with type 2 diabetes. And the reduction of expression of these genes play crucial roles in the pathogenesis of insulin resistance. Moreover,microRNAs expression are dysregulated in NAFLD,which are involved in metabolic regulation of glucose homeostasis and lipid metabolism. Thus, epigenetic modification plays a critical role in the pathogensis of NAFLD and the related glucose and lipid metabolism disorders.