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

Metabolic dysfunction-associated steatotic liver disease (MASLD) primarily results from dysregulated lipid metabolism in hepatocytes. However, the mechanisms governing hepatic lipid metabolism remain incompletely understood. Our preliminary experiments demonstrated elevated expression of R-spondin 2 (RSPO2), a matricellular protein, in steatotic livers. To investigate the role of RSPO2 in MASLD and the potential mechanisms involved, we performed bulk RNA sequencing of liver samples from Apoe knockout mice injected with either control Gfp-AAV or Rspo2-AAV to induce RSPO2 overexpression, following 12 weeks of Western diet feeding.