title: Prebiotic approach alleviates hepatic steatosis: implication of fatty acid oxidative and cholesterol synthesis pathways.
abstract: METHODS
  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.
  
  
  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.
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Pachikian
authors.forename: Ahmed
authors.initials: A
authors.lastname: Essaghir
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Demoulin
authors.forename: Emilie
authors.initials: E
authors.lastname: Catry
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Neyrinck
authors.forename: Evelyne M
authors.initials: EM
authors.lastname: Dewulf
authors.forename: Florence M
authors.initials: FM
authors.lastname: Sohet
authors.forename: Laurence
authors.initials: L
authors.lastname: Portois
authors.forename: Laure-Alix
authors.initials: LA
authors.lastname: Clerbaux
authors.forename: Yvon A
authors.initials: YA
authors.lastname: Carpentier
authors.forename: Sam
authors.initials: S
authors.lastname: Possemiers
authors.forename: Guido T
authors.initials: GT
authors.lastname: Bommer
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delzenne
mesh_terms: D000818:Animals; D001644:Bifidobacterium / Q000254:growth & development; D002784:Cholesterol / Q000096:biosynthesis*; D019587:Dietary Supplements; D002149:Energy Intake; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology*; D041981:Gastrointestinal Tract / Q000382:microbiology; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D054892:Metagenome / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D009844:Oligosaccharides / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D056692:Prebiotics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015525:Fatty Acids, Omega-3; D009844:Oligosaccharides; D047493:PPAR alpha; D056692:Prebiotics; C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; C116580:fructooligosaccharide; D052216:Glucagon-Like Peptide 1; D002784:Cholesterol