R-spondin 2 suppresses hepatic steatosis via activation of AMPK-ACC signaling

Given the hepatic/extrahepatic complications associated with MASLD (metabolic dysfunction-associated steatotic liver disease) and its high prevalence, it is crucial to decipher the precise molecular mechanisms regulating its pathogenesis to identify novel druggable targets. In this study, we demonstrate for the first time that hepatocyte RSPO2 plays a protective role against hepatic steatosis, fibrosis, and inflammation. Rspo2 overexpression improves lipid metabolism, enhances AMPK-ACC signaling, and reduces hepatocyte apoptosis. Therefore, targeting RSPO2 in hepatocytes may represent a promising strategy to suppress MASLD.