Prebiotic approach alleviates hepatic steatosis: Implication of fatty acid oxidative and cholesterol synthesis pathways

Abstract

Scope Recent data suggest that gut microbiota contributes to the regulation of host lipid metabolism. We report how fermentable dietary fructo‐oligosaccharides (FOS) control hepatic steatosis induced by n‐3 PUFA depletion, which leads to hepatic alterations similar to those observed in non‐alcoholic fatty liver disease patients. Methods and results C57Bl/6J mice fed an n‐3 PUFA‐depleted diet for 3 months were supplemented with FOS during the last 10 days of treatment. FOS‐treated mice exhibited higher caecal Bifidobacterium spp. and lower Roseburia spp. content. Microarray analysis of hepatic mRNA revealed that FOS supplementation reduced hepatic triglyceride accumulation through a proliferator‐activated receptor α‐stimulation of fatty acid oxidation and lessened cholesterol accumulation by inhibiting sterol regulatory element binding protein 2‐dependent cholesterol synthesis. Cultured precision‐cut liver slices confirmed the inhibition of fatty acid oxidation. FOS effects were related to a decreased hepatic micro‐RNA33 expression and to an increased colonic glucagon‐like peptide 1 production. Conclusions The changes in gut microbiota composition by n‐3 PUFA‐depletion and prebiotics modulate hepatic steatosis by changing gene expression in the liver, a phenomenon that could implicate micro‐RNA and gut‐derived hormones. Our data underline the advantage of targeting the gut microbiota by colonic nutrients in the management of liver disease.