An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
Journal article, 2018

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. Mardinoglu et al. use multi-omics to investigate the effects of a carbohydrate-restricted diet in obese NAFLD patients. They show that the diet improves liver fat metabolism, promotes rapid shifts in the gut microbiota, increases circulating folate, and upregulates expression of genes involved in folate-dependent one-carbon metabolism in the liver.

inflammation

NAFLD

microbiome

PPAR-α

carbohydrate-restricted diet

Streptococcus

folate

β-oxidation

FGF21

multi-omics

Author

Adil Mardinoglu

Royal Institute of Technology (KTH)

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Hao Wu

University of Gothenburg

Elias Björnson

University of Gothenburg

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

C. Zhang

Royal Institute of Technology (KTH)

A. Hakkarainen

Helsinki University Central Hospital

Sari M. Räsänen

University of Helsinki

Sunjae Lee

Royal Institute of Technology (KTH)

Rosellina M. Mancina

University of Gothenburg

Mattias Bergentall

University of Gothenburg

K. H. Pietilainen

Helsinki University Central Hospital

University of Helsinki

S. Soderlund

University of Helsinki

Niina Matikainen

Helsinki University Central Hospital

University of Helsinki

Marcus Ståhlman

University of Gothenburg

Per Olof Bergh

University of Gothenburg

Martin Adiels

University of Gothenburg

B. D. Piening

Stanford University

Marit Granér

University of Helsinki

N. Lundbom

Helsinki University Central Hospital

Kevin J. Williams

University of Gothenburg

S. Romeo

University of Gothenburg

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

M. Snyder

Stanford University

Mathias Uhlen

Royal Institute of Technology (KTH)

Göran Bergström

University of Gothenburg

Rosie Perkins

University of Gothenburg

H. U. Marschall

University of Gothenburg

Fredrik Bäckhed

University of Gothenburg

Marja Riitta Taskinen

University of Helsinki

Jan Borén

University of Gothenburg

Cell Metabolism

1550-4131 (ISSN)

Vol. 27 3 559-571.e5

Subject Categories

Other Clinical Medicine

Food Science

Nutrition and Dietetics

DOI

10.1016/j.cmet.2018.01.005

More information

Latest update

1/17/2019