Prebiotic and Symbiotic Modifications of Beta Oxidation and Lipogenic Gene Expression After Experimental Hypercholesterolemia in Rat Liver

Abstract

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is characterized by the presence of fat in hepatocytes because of decreased ß-oxidation and increased lipogenesis. Prebiotics, probiotics, and symbiotics have modulatory effects on intestinal microbiota and may influence the gut-liver axis. Our aim was to evaluate the effects of prebiotics, probiotics, and symbiotics on liver histopathology and gene expression related to ß-oxidation and lipogenesis after hypercholesterolemia. Methods: Wistar male adult rats (n=40) were submitted to hypercholesterolemic conditions (HPC) (60 days). On Day 30 of HPC, rats were subdivided in 5 groups: negative control (NC): without HPC + Gv (distilled water); positive control (PC): with HPC + Gv (distilled water); prebiotic (PRE): HPC + Gv with prebiotic (Fiber FOS®); probiotic (PRO): HPC + Gv with probiotic strains Gv (Probiatop®)); and symbiotic (SYM): HPC + Gv with symbiotic (Simbioflora®). All rats were sacrificed on Day 30 post-treatment. Blood was collected to verify total serum cholesterol, and liver tissue was sampled to verify histopathological changes and gene expression. Gene expression related to ß-oxidation (PPAR-± and CPT-1) and lipogenesis (SREBP-1c, FAS and ME) was evaluated in liver tissue using RT-qPCR. Results: PC had higher cholesterol levels when compared to NC (p<0.009). PRE and SYN rats had lower cholesterol levels than PC (p<0.001). PC rats showed more histopathological changes than NC rats (p<0.05); PRE and SYM rats showed fewer alterations than PC rats (p<0.05). PPAR-± was expressed at higher levels in SYM and PC rats compared with PRE and PRO rats (p<0.004). CPT-1 expression was similar in all groups (p > 0.05). SREBP-1c was expressed at higher levels in PC rats compared with NC rats (p=0.009); levels were lower in SYM rats compared with PRO rats (P=0.002); levels were lower in PRE rats compared with PC and PRO rats (p<0.01). FAS was expressed at lower levels in PRE rats compared with SYM rats (p=0.043). ME expression was lower in PC rats compared with NC rats (p=0.026). Conclusions: Prebiotic and symbiotic supplementation improve hepatic alterations related to hypercholesterolemia. These changes appear to be mediated by altered expression of genes related to ß-oxidation and lipogenesis.Keywords: cholesterol diet, steatosis, rats, prebiotic, probiotic, symbiotic, gene expression (AU)