Vaspin attenuates steatosis-induced fibrosis via GRP78 receptor by targeting AMPK signaling pathway.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that is rapidly becoming a public health problem. An imbalance in lipid distribution to the hepatocytes and metabolism causes hepatocyte steatosis. Vaspin is a newly discovered adipokine that has been linked to a variety of metabolic disorders. The effects of vaspin on steatosis and fibrosis pathogenesis and related mechanisms are unclear. Thus, this study investigated the molecular mechanism of vaspin on hepatocyte steatosis and fibrosis. HepG2 cells were treated with 1.2 mM free fatty acid and the intracellular lipid values were measured by flow cytometry and Nile red assay. RT-qPCR was used to assess the effect of vaspin and blocking of the GRP78 receptor on the expression of lipogenesis, oxidation, uptake, and secretion of fatty acid (FA), as well as AMPK activity. In co-cultured HepG2 and LX-2 cell lines, the expression of main proteins of hepatocyte fibrosis was analyzed using Western blot analysis. In the HepG2 cell line, we discovered that vaspin increased oxidation, FA secretion and gene expression, and AMPK activity and decreased lipogenesis and FA uptake and gene expression. Western blot analysis in co-cultured HepG2 and LX-2 cell lines showed that α-SMA and TGF-β1 protein expression decreased. The data demonstrated that vaspin acts as a novel regulator of hepatocyte steatosis through the GRP78 receptor, effectively reducing hepatocyte fibrosis through AMPK activation and decreasing NF-κB gene expression.