Down-regulation of lncRNA-NEAT1 alleviated the non-alcoholic fatty liver disease via mTOR/S6K1 signaling pathway

Without effective medical interventions for complete reverse of NAFLD, it needs to urgently explore the underlying molecular mechanisms of non-alcoholic fatty liver disease (NAFLD) to offer a novel therapeutic strategy for people suffering from NAFLD. Sprague-Dawley (SD) rats were used to establish the NAFLD animal model. Lipofectamine 2000 was used to silence or over-express NEAT1. The expression of NEAT1 and the mRNA levels of ACC and FAS were determined by qRT-PCR. Western blot assays were performed to detect the expression of ACC and FAS at protein levels and the related protein levels of mTOR/S6K1 signaling pathway. The levels of liver triglyceride (TG), serum total cholesterol (TC), ALT, and AST were assessed by an automatic biochemistry analyzer. The levels of liver TG and serum cholesterol were obviously up-regulated in NAFLD rat model. The level of NEAT1 expression and the mRNA levels of ACC and FAS were obviously enhanced in NAFLD model both in vivo and in vitro. Knockdown of NEAT1 could also reduce the elevation of ACC and FAS induced by FFA in liver cells. Moreover, inhibition of mTOR/S6K1 pathway presented with the same effect with knockdown of NEAT1 on the expression of ACC and FAS mRNA levels. The injection of si-NEAT1 lentivirus was performed to treat NAFLD of rats and the obvious efficacy for NAFLD rats was achieved. In a word, the down-regulated level of NEAT1 could remit the non-alcoholic fatty liver disease through mTOR/S6K1 signaling pathway in rats. The level of lncRNA-NEAT1 and activation of mTOR signaling pathway were first-time proved to be increased in non-alcoholic fatty liver disease tissues and cells. NEAT1 could also promote the expression of ACC and FAS which took part in the synthesis of lipid in liver cells. Down-regulated level of NEAT1 was proved to remit the non-alcoholic fatty liver disease through mTOR/S6K1 signaling pathway.