Key result
Hepatocyte Fgl1 deletion in mice does not aggravate MASLD or HCC progression.
Why the study?
MASLD alters hepatokine secretion including FGL1, a candidate mediator of liver steatosis and hyperglycemia, but its contribution to liver disease required investigation.
Does hepatocyte-specific deletion of Fgl1 aggravate metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma in mice?
Does hepatocyte-specific deletion of Fgl1 aggravate metabolic dysfunction-associated steatotic liver disease and hepatocellular carcinoma in mice?
Hepatocyte-derived FGL1 deletion sensitizes mice to diet-induced glucose intolerance but does not significantly alter the progression of MASLD or HCC, suggesting FGL1 is not a major contributor to their pathogenesis.
Hepatocyte FGL1 ablation does not worsen steatosis or HCC in mice; leaves open its relevance as a therapeutic target in human MASLD.
Metabolic dysfunction-associated steatotic liver disease (MASLD) begins with simple steatosis, which can progress to hepatocellular carcinoma (HCC). The pathogenesis 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 higher levels of plasma glucose, 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.
No takes yet. Share an insight, caveat, or question.
Personnaz et al. (2024) studied Metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). Hepatocyte-specific deletion of Fgl1 vs. Wild-type mice (Fgl1LWT) was evaluated on Liver lipid deposition and HCC progression. Hepatocyte-specific deletion of Fgl1 in mice did not aggravate liver lipid deposition or HCC progression compared to wild-type mice, suggesting FGL1 is not a major contributor to MASLD and HCC.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: