Mardinoglu, AdilWu, HaoBjornson, EliasZhang, ChengHakkarainen, AnttiRäsänen, Sari M.Lee, SunjaeMancina, Rosellina M.Bergentall, MattiasPietiläinen, Kirsi H.Söderlund, SanniMatikainen, NiinaStahlman, MarcusBergh, Per-OlofAdiels, MartinPiening, Brian D.Graner, MaritLundbom, NinaWilliams, Kevin J.Romeo, StefanoNielsen, JensSnyder, MichaelUhlen, MathiasBergstrom, GoranPerkins, RosieMarschall, Hanns-UlrichBackhed, FredrikTaskinen, Marja-RiittaBoren, Jan2018-04-042018-04-042018-03-06Mardinoglu, A, Wu, H, Bjornson, E, Zhang, C, Hakkarainen, A, Räsänen, S M, Lee, S, Mancina, R M, Bergentall, M, Pietiläinen, K H, Söderlund, S, Matikainen, N, Stahlman, M, Bergh, P-O, Adiels, M, Piening, B D, Graner, M, Lundbom, N, Williams, K J, Romeo, S, Nielsen, J, Snyder, M, Uhlen, M, Bergstrom, G, Perkins, R, Marschall, H-U, Backhed, F, Taskinen, M-R & Boren, J 2018, 'An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans', Cell Metabolism, vol. 27, no. 3, pp. 559-+. https://doi.org/10.1016/j.cmet.2018.01.005ORCID: /0000-0002-6229-3588/work/90757069ORCID: /0000-0003-0041-1240/work/94378174ORCID: /0009-0001-5883-2446/work/156156235http://hdl.handle.net/10138/233915A 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.18engunspecifiedinfo:eu-repo/semantics/openAccessNONALCOHOLIC FATTY LIVERGROWTH-FACTOR 21VERY-LOW-CARBOHYDRATEINSULIN-RESISTANCEWEIGHT-LOSSLIPID-METABOLISMGUT MICROBIOTAPPAR-ALPHAFOLATE-DEFICIENCYGLUTATHIONE METABOLISMBiochemistry, cell and molecular biologyGeneral medicine, internal medicine and other clinical medicineArticleopenAccess7e498e1c-7df5-4322-8caa-47348a5262c485041993278000426936200010