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An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
KTH, Centres, Science for Life Laboratory, SciLifeLab.
KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-8640-9370
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2018 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 27, no 3, p. 559-571.e5Article in journal (Refereed) Published
Abstract [en]

A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum beta-hydroxybutyrate concentrations, reflecting increased mitochondrial beta-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Liver transcriptomic analysis on biopsy samples from a second cohort revealed downregulation of the fatty acid synthesis pathway and upregulation of folate-mediated one-carbon metabolism and fatty acid oxidation pathways. Our results highlight the potential of exploring diet-microbiota interactions for treating NAFLD.

Place, publisher, year, edition, pages
Cell Press , 2018. Vol. 27, no 3, p. 559-571.e5
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:kth:diva-225191DOI: 10.1016/j.cmet.2018.01.005ISI: 000426936200010PubMedID: 29456073Scopus ID: 2-s2.0-85041993278OAI: oai:DiVA.org:kth-225191DiVA, id: diva2:1195103
Funder
Swedish Research CouncilSwedish Heart Lung FoundationSwedish Diabetes AssociationEU, FP7, Seventh Framework Programme, 305707EU, European Research Council, 615362 - META-BASETorsten Söderbergs stiftelseScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180404

Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-04Bibliographically approved

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Mardinoglu, AdilZhang, Cheng

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