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Cell Metab. 2018 Mar 6;27(3):559-571.e5. doi: 10.1016/j.cmet.2018.01.005. Epub 2018 Feb 15.

An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans.

Author information

1
Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden; Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
2
Department of Molecular and Clinical Medicine, University of Gothenburg, and Sahlgrenska University Hospital, Gothenburg, Sweden.
3
Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Department of Molecular and Clinical Medicine, University of Gothenburg, and Sahlgrenska University Hospital, Gothenburg, Sweden.
4
Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
5
HUS Medical Imaging Center, Radiology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
6
Research Programs Unit, Diabetes and Obesity, University of Helsinki and Department of Internal Medicine, Helsinki University Hospital, Helsinki, Finland.
7
Research Programs Unit, Diabetes and Obesity, University of Helsinki and Department of Internal Medicine, Helsinki University Hospital, Helsinki, Finland; Endocrinology, Abdominal Center, Helsinki University Hospital, Helsinki, Finland.
8
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
9
Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
10
Department of Molecular and Clinical Medicine, University of Gothenburg, and Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: fredrik.backhed@wlab.gu.se.
11
Department of Molecular and Clinical Medicine, University of Gothenburg, and Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: jan.boren@wlab.gu.se.

Abstract

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 β-hydroxybutyrate concentrations, reflecting increased mitochondrial β-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.

KEYWORDS:

FGF21; NAFLD; PPAR-α; Streptococcus; carbohydrate-restricted diet; folate; inflammation; microbiome; multi-omics; β-oxidation

PMID:
29456073
DOI:
10.1016/j.cmet.2018.01.005

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