Prebiotic approach alleviates hepatic steatosis: Implication of fatty acid oxidative and cholesterol synthesis pathways
Article first published online: 2 DEC 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 57, Issue 2, pages 347–359, February 2013
How to Cite
Pachikian, B. D., Essaghir, A., Demoulin, J.-B., Catry, E., Neyrinck, A. M., Dewulf, E. M., Sohet, F. M., Portois, L., Clerbaux, L.-A., Carpentier, Y. A., Possemiers, S., Bommer, G. T., Cani, P. D. and Delzenne, N. M. (2013), Prebiotic approach alleviates hepatic steatosis: Implication of fatty acid oxidative and cholesterol synthesis pathways. Mol. Nutr. Food Res., 57: 347–359. doi: 10.1002/mnfr.201200364
- Issue published online: 22 JAN 2013
- Article first published online: 2 DEC 2012
- Manuscript Accepted: 16 OCT 2012
- Manuscript Revised: 21 SEP 2012
- Manuscript Received: 8 JUN 2012
- Région Wallonne
- Gut microbiota;
- micro-RNA 33;
- Peroxisome proliferator-activated receptor;
- Sterol regulatory element binding protein
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.
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.