Pirfenidone ameliorates MAFLD by improving insulin sensitivity and reducing epididymal fat

Introduction and Objectives

Metabolic associated fatty liver disease (MAFLD) is characterized by hepatic steatosis with the following three metabolic conditions: obesity/overweight, diabetes and metabolic dysregulation, either alone or in combination. Pirfenidone (PFD) has anti-inflammatory, antioxidant, and anti-fibrotic effects. The aim of this study was to investigate the effects of PFD in mice with MAFLD induced by high-fat/high-carbohydrate (HFHC) diet.

Materials and methods

At the age of 6-7 weeks, six male C57BL/6 J mice were fed with a normal diet (ND, 18% kcal from fat food) and twelve with HFHC (60% kcal from fat food and drinking water with 42 g/L of carbohydrates: 55% fructose and 45% sucrose) diet for 20 weeks; at 10 weeks of feeding, six mice with HFHC diet were administered PFD (300 mg/kg/day) by gavage. An insulin tolerance test was performed, and data analysis were performed using SPSS. The trial was approved by the research ethics committee.

Results

All HFHC mice showed an increase in body weight and visceral fat accumulation (P<0.01), including elevated fasting glucose at week 20 (P<0.001). Liver weight and liver/body weight ratio exhibited no statistical significance. HFHC mice intervened with PFD showed reduced body weight gain (P=0.054) and epididymal fat pad weight (P<0.05). PFD also improved insulin resistance.

Discussion

Obesity, systemic insulin resistance, and diabetes are commonly associated with MAFLD, which may progress to nonalcoholic steatohepatitis (NASH). PFD has been shown to have benefits in models of lipotoxicity and NASH.

Conclusions

PFD could be a promising drug for the prevention and treatment of MAFLD induced by obesity.

Funding

The resources used in this study were from the hospital without any additional financing

Declaration of interest

The authors declare no potential conflicts of interest.