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

Mol Nutr Food Res. 2013 Feb;57(2):347-59. doi: 10.1002/mnfr.201200364. Epub 2012 Dec 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bifidobacterium / growth & development
  • Cholesterol / biosynthesis*
  • Dietary Supplements*
  • Energy Intake
  • Fatty Acids, Omega-3 / metabolism*
  • Fatty Liver / metabolism
  • Fatty Liver / pathology*
  • Gastrointestinal Tract / microbiology
  • Gene Expression Regulation
  • Glucagon-Like Peptide 1 / genetics
  • Glucagon-Like Peptide 1 / metabolism
  • Lipid Metabolism
  • Liver / metabolism
  • Male
  • Metagenome / physiology
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease
  • Oligosaccharides / administration & dosage
  • Oxidative Stress / drug effects
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • Prebiotics*
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Sterol Regulatory Element Binding Protein 2 / genetics
  • Sterol Regulatory Element Binding Protein 2 / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Fatty Acids, Omega-3
  • Oligosaccharides
  • PPAR alpha
  • Prebiotics
  • Srebf1 protein, mouse
  • Srebf2 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Sterol Regulatory Element Binding Protein 2
  • Transcription Factors
  • fructooligosaccharide
  • Glucagon-Like Peptide 1
  • Cholesterol