Effect of microRNA-486 on alcoholic fatty liver disease in mice

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Objective To investigate the effect of microRNA-486 (miR-486) on alcoholic fatty liver disease in mice. Methods The progenies of miR-486 knockout mice were obtained by mating of heterozygotes. The 8-week-old progenies were divided into miR-486 knockout control group (KO-PAIR group), miR-486 knockout experimental group (KO-ETOH group), wild type control group (WT-PAIR group) and wild type experimental group (WT-ETOH group), 8 mice in each group. Th mice in experimental group were fed on 5% TP4030D alcohol feed, and those in TP4030C control group were fed on control feed for 4 weeks, 15 ml/mouse per day. On the last day of the experiment, the alcohol group was given alcohol (31.5%) intragastrically, and the control group was administered with dextrin, 100 μl each mouse. After 9 h, the mice were sacrificed and their liver tissues and serum were collected. Liver tissue sections were stained with hematoxylin-eosin (HE) and saturated oil red O. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and tumor necrosis factor-α (TNF-α) were determined. The mRNA and protein expression levels of lipid metabolism related molecules adenosine monophosphate-activated protein kinase (AMPK) and acetyl-coA carboxylase-ser 79 (ACC) were detected by real-time fluorescence quantitative polymerization chain reaction and Western blotting, respectively. The severity of alcoholic fatty liver disease was evaluated and the mechanism was explored. Results HE staining and saturated oil red O staining showed that liver fatification was significantly aggravated in the WT-ETOH group as compared with the KO-ETOH group. As compared with the WT-ETOH group, serum levels of ALT, AST and TNF-α in the KO-ETOH group were significantly reduced [(124.875±38.591) U/L vs. (45.500±20.333) U/L, (190.750±23.789) U/L vs. (140.625±31.794) U/L, and (73.407±17.121) μg/L vs. (50.056±12.717) μg/L, F=32.503, 5.876 and 30.865, P<0.05]. The mRNA level of AMPK in the KO-ETOH group was significantly higher (0.61±0.09 vs. 1.06±0.11, F=21.249, P<0.01), and that of ACC was significantly lower (1.98±0.23 vs. 1.23±0.12, F=68.584, P<0.01) than in the WT-ETOH group, which was further confirmed by Western blotting (0.77±0.09 vs. 1.20±0.08, and 1.16±0.13 vs. 0.38±0.08, P<0.01). Conclusion Deficiency of miR-486 can alleviate alcoholic fatty liver disease in mice probably by regulating lipid metabolism. Key words: MicroRNA-486; Alcoholic fatty liver disease; Lipid metabolism