Effect of miR-34a in regulating steatosis by targeting PPARα expression in nonalcoholic fatty liver disease

被引:218
作者
Ding, Jiexia [1 ]
Li, Meng [2 ]
Wan, Xingyong [2 ]
Jin, Xi [2 ]
Chen, Shaohua [2 ]
Yu, Chaohui [2 ]
Li, Youming [2 ]
机构
[1] Hangzhou First Peoples Hosp, Dept Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China
[2] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Gastroenterol, Hangzhou 310003, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
ACTIVATED-RECEPTOR-ALPHA; PROTEIN-KINASE; MICRORNAS; ACID; MICE; METABOLISM; STEATOHEPATITIS; OXIDATION; SEVERITY;
D O I
10.1038/srep13729
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
MicroRNA-34a (miR-34a) is thought to be involved in nonalcoholic fatty liver disease (NAFLD). However, the association between altered expression of miR-34a and the pathophysiological features of NAFLD remains unclear. Here, we investigated the mechanisms by which miR-34a influences NAFLD through the PPAR alpha-related pathway. Real-time quantitative PCR, western blotting and other assays kit were used to investigate the expression and function of miR-34a in an NAFLD model. Cultured cells transfected with miR-34a inhibitor and C57BL/6 mice injected with the miR-34a inhibitor through vein tail were conducted for the effects of miR-34a on its target. MiR-34a levels were significantly upregulated in steatosis-induced hepatocytes and in liver tissues of high-fat diet-fed mice. The upregulation of miR-34a resulted in the downregulation of hepatic PPAR alpha and SIRT1 that are the direct targets of miR-34a. Silencing miR-34a led to an initially increased expression of PPAR alpha, SIRT1 and PPAR alpha's downstream genes. Activation of the central metabolic sensor AMPK was also increased. The miR-34a inhibitor suppressed lipid accumulation and improved the degree of steatosis. Taken together, our data indicated that decreased expression of miR-34a potentially contributes to altered lipid metabolism in NAFLD. Downregulation of miR-34a may be a therapeutic strategy against NAFLD by regulating its target PPAR alpha and SIRT1.
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页数:10
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