Ablation of Hepatocyte Derived-FGL1 Does Not Aggravate Metabolic Dysfunction-Associated Steatotic Liver Disease

Area of Science:

• Hepatology
• Metabolic Diseases
• Oncology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) progresses from simple steatosis to hepatocellular carcinoma (HCC).
• Fibrinogen-like 1 (FGL1), a hepatokine, is implicated in liver steatosis and hyperglycemia.
• The role of FGL1 in MASLD pathogenesis requires further investigation.

Purpose of the Study:

• To determine the contribution of hepatocyte-specific FGL1 to MASLD and HCC development.
• To compare the effects of FGL1 deficiency on metabolic alterations and liver injury.

Main Methods:

• Hepatocyte-specific Fgl1-deficient mice and wild-type littermates were used.
• Mice were subjected to experimental protocols for steatosis (Western diet) and HCC.
• Metabolic parameters, liver steatosis, and liver injury markers were assessed.

Main Results:

• FGL1-deficient mice exhibited increased plasma glucose and metabolic dysfunction on a Western diet.
• Despite metabolic changes, FGL1 deficiency did not alter liver lipid deposition in steatosis models.
• Liver alterations during HCC progression were similar between wild-type and FGL1-deficient mice.
• FGL1 expression decreased with MASLD severity in mice and humans.

Conclusions:

• Hepatocyte-specific FGL1 is not a major contributor to the pathogenesis of MASLD.
• FGL1 does not play a significant role in the progression of diet-induced liver steatosis or experimental HCC.
• FGL1 repression correlates with liver injury severity during MASLD progression.