ROLE OF FGL1 IN LIVER-RELATED METABOLIC DISEASES

Metabolic associated steatotic liver disease (MASLD) is the hepatic manifestation of the metabolic syndrome that affects 30% of the adult worldwide population. MASLD is a pathological cascade that starts from a benign steatosis and evolves toward nonalcoholic steatohepatitis (MASH) and hepatocellular carcinoma (HCC). While the steatosis and MASH stages are reversible, the cirrhosis stage is irreversible and life threatening. Current treatments against HCC are largely inefficient. A better understanding of the mechanisms involved in this pathological cascade is a prerequisite to envision the development of new therapeutic strategies. Evidence in the literature indicate that the recently described hepcidin suppressor FGL1 contributes to the progression of steatosis and HCC but its function in the pathogenesis of MASLD is unknown. We therefore explored the potential contribution of FGL1 to the pathogenesis of liver diseases.

 

Mice with specific deletion of Fgl1 deletion in hepatocytes (Fgl1-LKO) were fed a western diet for 16 weeks to induce a MASH-like phenotype. Circulating levels of triglycerides, cholesterol, free fatty acids and transaminases were measured at 16 weeks and liver steatosis and fibrosis was analyzed on histological tissue sections. Mice deficient for Fgl1 exhibited impaired glucose tolerance and increased circulating lipids and transaminases concentration.

 

While the histological analysis is ongoing, these results suggest that FGL1 exerts a protective function against liver injury and may be a relevant therapeutic target for the management of the transition from MASH to HCC.