Additionally, in liver disease studies, CREG1 was reported to inhibit hepatic steatosis and metabolic disorders in high-fat-diet (HFD)-fed mice through direct interaction with apoptosis signal-regulating kinase 1 (ASK1) and inactivation of ASK1-c-Jun N-terminal kinase (JNK1) signalling; CREG1 was also found to protect against cell death and inflammation during hepatic ischemia-reperfusion (I/R) injury in a TGF-β-activated kinase 1 (TAK1)-dependent manner 17, 18. This evidence concerns the gene MAPK8 and Other metabolic disease.