Testing the contribution of fibrinogen like 1 to the pathogenesis of metabolic dysfunction associated steatotic liver disease and hepatocellular carcinoma

Metabolic dysfunction associated steatotic liver disease (MASLD) initiates from a simple steatosis that can evolve into hepatocellular carcinoma (HCC). The pathogensis of MASLD alters the secretion of hepatokines such as fibrinogen-like 1 (FGL1), a candidate mediator of liver steatosis and hyperglycemia. To investigate the contribution of FGL1 to liver diseases, we compared wild-type mice to mice with hepatocyte specific deletion of Fgl1 subjected to a steatosis or HCC experimental protocol. We found that mice deficient for Fgl1 in hepatocytes showed a reduced tolerance to glucose with pronounced metabolic alterations and liver injury when fed a western diet compared to their wild-type counterparts. However, both genotypes exhibited a similar lipid deposition in the liver. Similarly, wild type and Fgl1 deficient mice displayed comparable liver alterations during HCC progression. We observed that FGL1 expression was repressed during MASLD progression in mice and human concomitantly with the severity of liver injury. Altogether, these findings suggest that FGL1 is not a major contributor to the pathogenesis of MASLD and HCC.