Glutathione S-transferase Mu 2 inhibits hepatic steatosis via ASK1 suppression

Abstract

AbstractHepatic steatosis is the main characteristic of some liver metabolism diseases. However, unclear molecular mechanism of hepatic steatosis impedes the therapy of this hepatic steatosis. Glutathione-S-transferase mu 2 (GSTM2), as a member of phase II drug metabolizing enzymes (DMEs), regulates cellular antioxidant and detoxificant.GSTM2was highly up-regulated in hepatic steatosis tissues and high-fat diet (HFD) fed mice. Loss-of-functionGSTM2mouse model demonstrated thatGSTM2protected mice from excess fat accumulation. Mechanistically,GSTM2interacted with ASK1 and suppressed its phosphorylation and the activation of subsequent downstream p38-JNK signalling. Moreover,GSTM2overexpression in the liver effectively ameliorated hepatic lipid accumulation. Therefore, we identifiedGSTM2as an important negative regulator in progression of hepatic steatosis via both its detoxification/antioxidant and inhibition of ASK1-p38/JNK signalling. This study showed potential therapeutic function of the DME in progression of hepatic steatosis.