Molecular mechanisms of hepatic insulin resistance in nonalcoholic fatty liver disease and potential treatment strategies.

The prevalence of nonalcoholic fatty liver disease (NAFLD) in the general population is estimated at 25 %, and there is currently no effective treatment of NAFLD. Although insulin resistance (IR) is not the only factor causing the pathogenesis of NAFLD, hepatic IR has a cause-effective relationship with NAFLD. Improving hepatic IR is a potential therapeutic strategy to treat NAFLD. This review highlights the molecular mechanisms of hepatic IR in the development of NAFLD. Available data on potential drugs including glucagon-like peptide 1 receptor (GLP-1) agonists, peroxisome proliferator-activated receptor (PPAR-γ/α/δ) agonists, farnesoid X receptor (FXR) agonists, etc. are carefully discussed.

Gegen Qinlian Decoction abates nonalcoholic steatohepatitis associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of toll-like receptor 4 signaling pathways.

Gegen Qilian Decoction (GGQLD) is a well-established classic Chinese medicine prescription in treating nonalcoholic steatohepatitis (NASH). However, the molecular mechanism of GGQLD action on NASH is still not clear. This study aimed to assess the anti-NASH effect of GGQLD, and to explore its molecular mechanisms in vivo and in vitro. In HFD-fed rats, GGQLD decreased significantly serum triglyceride (TG), cholesterol (CHO), total bile acid (TBA), low-density lipoprotein (LDL), free fatty acid (FFA) and lipopolysaccharide (LPS) levels, increased levels of differentially expressed proteins (DEPs) Ahcy, Gpx1, Mat1a, GNMT, and reduced the expression of ALDOB. In RAW264.7 macrophages, GGQLD reduced the expression levels of inflammatory factors TNF-α and IL-6 mRNA, and diminished NASH by increasing differentially expressed genes (DEGs) CBS, Mat1a, Hnf4α and Pparα to reduce oxidative stress or lipid metabolism. The results of DEGs verification also showed that GGQLD up-regulated expressions of Hnf4α, Pparα and Cbs genes. In HepG2 cells, GGQLD decreased IL-6 levels and intracellular TG content, and inhibited FFA-induced expression of toll-like receptor 4 (TLR4). In summary, GGQLD abates NASH associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of TLR4 signal pathways. These findings provide new insights into the anti-NASH therapy by GGQLD.