Gallic acid ameliorates diabetic steatohepatitis in db/db mice fed with a high-fat diet

Abstract

The term nonalcoholic fatty liver disease has been changed to metabolic dysfunction–associated steatotic liver disease (MASLD). MASLD and metabolic dysfunction–associated steatohepatitis (MASH) are complications arising from increased lipid accumulation in the liver. Previous studies have indicated that gallic acid (GA) induces immune modulation. In this study, we examined the effectiveness of GA in reducing serum lipid levels and lipid deposition in the liver and ameliorating steatohepatitis in a diabetic mouse model fed with a high-fat diet (HFD). Animal studies were conducted using db/m mice as the normal control group and db/db mice fed with a normal diet, db/db mice fed with an HFD, and db/db mice fed with an HFD supplemented with GA as the study groups. The serum parameters were higher in the db/db group than in the normal control group. The serum lipid profiles and liver fatty scores were significantly higher in the HFD group than in the db/m and db/db groups. However, the levels of liver antioxidants were significantly lower in the HFD group than in the db/m and db/db group. When diabetic mice were fed with both an HFD and GA, an improvement was observed in the serum lipid profiles and liver fatty deposition, with the amelioration of steatohepatitis and enhancement of liver antioxidant activity. GA inhibits MASH by upregulating the expression of miR-30a-3p and downregulating the expression of NF-κB. GA also increases the levels of antioxidant enzymes and ameliorates MASH in HFD-fed diabetic mice.

Keywords

• Diabetes mellites
• Metabolic dysfunction–associated steatotic liver disease
• Metabolic dysfunction–associated steatohepatitis
• gallic acid