Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease characterized by ectopic lipid accumulation in hepatocytes. To date, no specific drug has been approved for its treatment. Metabotropic glutamate receptor 5 (mGluR5) has been showed expressed in hepatocytes and related to some liver diseases such as alcoholic steatosis. However, the function of mGluR5 in NAFLD is not clear. This work aims to investigate the effect and potential mechanism of mGluR5 in NAFLD. We found that mGluR5 expression was increased in the livers of HFD-fed mice and in palmitate-treated HepG2 cells. Suppression of mGluR5 by the specific antagonist MPEP could ameliorate palmitate-induced lipid accumulation, whereas the mGluR5 agonist CHPG promoted lipid deposition in the cells. Knockdown of mGluR5 by small interfering RNA further demonstrated that inhibition of mGluR5 could reduce lipid accumulation. Furthermore, our results revealed that mGluR5 regulated lipid metabolism by increasing the gene expression of lipogenesis. Inflammatory factors and phosphorylation levels of NF-κB-p65 and JNK were also tested in treated hepatocytes. mGluR5 promoted the inflammatory reaction and JNK phosphorylation. Inhibition of JNK signaling by JNK-IN-8 rescued CHPG-induced lipogenesis and inflammation. This study showed mGluR5 regulated lipid accumulation and inflammation in palmitic acid-treated HepG2 cells via the JNK signaling pathway. mGluR5 might be a potential drug target for NAFLD.
Keywords: Inflammation; JNK; Lipogenesis; Metabotropic glutamate receptor 5; Nonalcoholic fatty liver disease.
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