HEPATIC ALTERATIONS IN EXPERIMENTAL METABOLIC SYNDROME: METFORMIN AND NARINGIN REVERSION

MARÍA AGUSTINA RIZZI; MAZO TAMARA; NORI TOLOSA DE TALAMONI; RODRÍGUEZ VALERIA

Mar de Plata

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS 2024 LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2023

Fructose-rich diets (FRD) are responsible for an increasein obesity and metabolic syndrome (MS) cases, many ofwhich may develop into non-alcoholic fatty liver disease(NAFLD). Metformin (Met) is used for the treatment ofinsulin resistance associated with MS but some clinicalstudies showed little effect of Met on the histological char-acteristics of the liver. Naringin (NAR) is a flavonoid withantioxidant, antiapoptotic, and anti-inflammatory proper-ties. Our purpose was to evaluate the effect of co-admin-istration of Met+NAR on systemic and metabolic alter-ations leading to NAFLD in animals with MS. Male Wistarrats were divided in 5 groups: 1) controls (C); 2) FRD 10%(w/v) in drinking water, 60 days; 3) FRD+Met (100 mg/kgb.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 param-eters were measured. Fatty acid (FA) profile and geneexpression of acetyl COA carboxylase (ACAC) and stea-royl-CoA desaturase 1 (SCD1) were determined in theliver. ANOVA/Bonferroni (p<0.05) was used for statisticalanalysis. Body weight and waist circumference were sig-nificantly higher in FRD rats compared to C rats. All treat-ments decreased waist circumference. Adiposity, hep-atosomatic index, and epididymal fat increased in FRDanimals, effects that were reversed with Met+NAR. FRDanimals had higher levels of TG/HDL ratio, AST, and LDHenzyme activities; NAR and combined treatment reducedthese parameters. Also, liver fibrosis was attenuated byMet+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 andSCD1 gene expression increased in FRD rats comparedto C group and decreased with the treatments. In con-clusion, Met+NAR could be used as a new therapeuticalternative for the treatment of NAFLD, as it reversesbiochemical and histological alterations and liver fibrosis,altered in this pathology.