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) 19327420 (eISSN)
Vol. 27 3 559-571.e5Subject Categories
Other Clinical Medicine
Food Science
Nutrition and Dietetics
DOI
10.1016/j.cmet.2018.01.005