xperimental fructose-induced non alcoholic fatty liver disease: metformin and naringin reversion

Abstract

Fructose-rich diets (FRD) produces metabolic disturbances characteristic of metabolic syndrome (MS), which leads to non-alcoholic fatty liver disease (NAFLD). Our purpose was to evaluate the effect of co-administration of metformin (Met) plus naringin (NAR) on systemic and metabolic alterations leading to NAFLD in animals with MS.

Male Wistar rats were divided in 5 groups: 1) controls (C); 2) FRD 10% (w/v) in drinking water, 60 days; 3) FRD+Met (100 mg/kg b.w.); 4) FRD+NAR (40 mg/kg b.w.); 5) FRD+Met+NAR. Treatments started on day 21 of FRD administration. Biometric, serum biochemical and liver structure parameters were measured. Fatty acid (FA) profile and gene expression of acetyl COA carboxylase (ACAC) and stearoyl-CoA desaturase 1 (SCD1) were determined in the liver. ANOVA/Bonferroni (p<0.05) was used for statistical analysis.

Body weight and waist circumference were significantly higher in FRD rats compared to C rats. All treatments decreased waist circumference. Adiposity, hepatosomatic index, and epididymal fat increased in FRD animals, effects that were reversed with Met+NAR. FRD animals had higher levels of TG/HDL ratio, AST, and LDH enzyme activities; NAR and combined treatment reduced these parameters. Also, liver fibrosis was attenuated by Met+NAR. Palmitic acid, monounsaturated FA and ω6/ω3 ratio were higher in FRD rats compared to C rats, while Met+NAR improved these parameters. ACAC and SCD1 gene expression increased in FRD rats compared to C group and decreased with the treatments.

In conclusion, Met+NAR could be used as a new therapeutic alternative for the treatment of NAFLD, as it reverses biochemical and histological alterations and liver fibrosis, altered in this pathology.