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Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
VTT Technical Research Centre of Finland, Espoo, Finland.
VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center A/S, Gentofte, Denmark.ORCID iD: 0000-0002-2856-9165
Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
2016 (English)In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 57, no 3, p. 474-481Article in journal (Refereed) Published
Abstract [en]

The gut microbiota influences many aspects of host metabolism. We have previously shown that the presence of a gut microbiota remodels lipid composition. Here we investigated how interaction between gut microbiota and dietary lipids regulates lipid composition in the liver and plasma, and gene expression in the liver. Germ-free and conventionally raised mice were fed a lard or fish oil diet for 11 weeks. We performed lipidomics analysis of the liver and serum and microarray analysis of the liver. As expected, most of the variation in the lipidomics dataset was induced by the diet, and abundance of most lipid classes differed between mice fed lard and fish oil. However, the gut microbiota also affected lipid composition. The gut microbiota increased hepatic levels of cholesterol and cholesteryl esters in mice fed lard, but not in mice fed fish oil. Serum levels of cholesterol and cholesteryl esters were not affected by the gut microbiota. Genes encoding enzymes involved in cholesterol biosynthesis were downregulated by the gut microbiota in mice fed lard and were expressed at a low level in mice fed fish oil independent of microbial status. In summary, we show that gut microbiota-induced regulation of hepatic cholesterol metabolism is dependent on dietary lipid composition.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2016. Vol. 57, no 3, p. 474-481
Keywords [en]
cholesterol/biosynthesis, fish oil, gene expression, germ-free, lipidomics, liver, microarrays
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-59367DOI: 10.1194/jlr.M065847ISI: 000371095500016PubMedID: 26783361Scopus ID: 2-s2.0-84963839186OAI: oai:DiVA.org:oru-59367DiVA, id: diva2:1136094
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Swedish Heart Lung FoundationTorsten Söderbergs stiftelseRagnar Söderbergs stiftelseNovo NordiskKnut and Alice Wallenberg Foundation
Note

Funding Agencies:

Human Frontier of Science Program

EU  FP7-KBBE-222639 

LUA-ALF grant from Vastra Götalandsregionen  

European Research Council (ERC)  615362-METABASE 

Available from: 2017-08-25 Created: 2017-08-25 Last updated: 2018-01-13Bibliographically approved

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Orešič, Matej

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