Chiglitazar, the first pan-PPAR agonist approved globally, shows potential to treat metabolic dysfunction–associated steatohepatitis in vitro and in vivo

Chiglitazar was approved by China's National Medical Products Administration (NMPA) in 2021 to treat patients with type 2 diabetes and potentially benefit patients with metabolic dysfunction–associated steatohepatitis (MASH). To investigate its efficacy in MASH, we performed monocyte activation and migration assays and liver and stellate cell proliferation assays in vitro, as well as conducted three different animal model studies of MASH in vivo. Our results showed that Chiglitazar significantly reduced the number of migrated cells of MCP-1 activated THP-1 cells. Furthermore, Chiglitazar-treated THP-1 cells showed reduced gene expression of TNF-α and MCP-1. Furthermore, Chiglitazar dramatically reduced the cell proliferation of TGF-β induced human skin fibroblasts and liver stellate cells, as well as reduced the gene expression of α-SMA and CTGF. In animal studies, Chiglitazar alleviated liver steatosis and inflammation in the MCD model and ameliorated liver inflammation and fibrosis in both the CCL4 and HFD+CCL4 models. In conclusion, as the first approved peroxisome proliferator-activated receptor (PPAR) agonist, Chiglitazar also shows potential to treat MASH by regulating steatosis, inflammation, and fibrosis. This potential could be translated into clinical studies in the future.