Journal
CELL METABOLISM
Volume 27, Issue 3, Pages 559-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2018.01.005
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Funding
- Swedish Research Council
- Swedish Heart-Lung Foundation
- Swedish Diabetes Foundation
- Sahlgrenska University Hospital ALF funds
- Sigrid Juselius Foundation
- Academy of Finland
- Finnish Diabetes Research Foundation
- EU Innovative Medicines Initiative EMIF
- FP7-HEALTH-INNOVATION-1 program RESOLVE [305707]
- European Research Council consolidator grant [615362 - META-BASE]
- Torsten Soderberg Professor in Medicine
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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.
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