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

Abstract

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.

Atorvastatin promotes AMPK signaling to protect against high fat diet‑induced non‑alcoholic fatty liver in golden hamsters

“…The pathogenesis of NAFLD is complex and involves numerous signaling pathways, including the PI3K/Akt, Toll-like receptor (TLR), apoptosis and mTOR pathways (43,44). Deficient PI3K activity leads to an increase in intracellular FA-derived metabolites (45).…”

Long noncoding RNA Hoxb3os is dysregulated in autosomal dominant polycystic kidney disease and regulates mTOR signaling

“…Another lncRNA, NEAT1, is up-regulated in nonalcoholic fatty liver disease and has been shown to influence the activation of mTOR. Overexpression of NEAT1 in cells increased the levels of p-mTOR and p-S6K, and inhibition of NEAT1 down-regulated mTOR signaling (45).…”

Long noncoding RNA NEAT1 suppresses hepatocyte proliferation in fulminant hepatic failure through increased recruitment of EZH2 to the LATS2 promoter region and promotion of H3K27me3 methylation

“…LncRNA NEAT1 was upregulated and LATS2 was downregulated in FHF A previous report showed that the expression of lncRNA NEAT1 was significantly increased in nonalcoholic fatty liver disease (NAFLD) models in vivo and in vitro, while downregulation of lncRNA NEAT1 alleviated NAFLD through the mammalian target of rapamycin/S6K1 signaling pathway 23 . In addition, it is also known that lncRNA NEAT1 accelerates the progression of hepatic fibrosis by regulating microRNA-122 and Kruppel-like factor 6 7 .…”

“…Our findings demonstrated that lncRNA NEAT1 was upregulated both in vivo and in vitro after D-GalN/LPS treatment, which was in accordance with the results from a previous study 30 . In addition, elevated expression of lncRNA NEAT1 has also been documented in NAFLD rat models and free fatty acidtreated rat hepatic cells 23 . Similarly, lncRNA NEAT1 is expressed at significantly high levels in tissues and cell lines of breast cancer, and its knockdown caused a decrease in cell proliferation and EZH2 expression 31 .…”