An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
Artikel i vetenskaplig tidskrift, 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

Författare

Adil Mardinoglu

Kungliga Tekniska Högskolan (KTH)

Chalmers, Biologi och bioteknik, Systembiologi

Hao Wu

Göteborgs universitet

Elias Björnson

Göteborgs universitet

Chalmers, Biologi och bioteknik, Systembiologi

C. Zhang

Kungliga Tekniska Högskolan (KTH)

A. Hakkarainen

Helsinki University Central Hospital

Sari M. Räsänen

Helsingin Yliopisto

Sunjae Lee

Kungliga Tekniska Högskolan (KTH)

Rosellina M. Mancina

Göteborgs universitet

Mattias Bergentall

Göteborgs universitet

K. H. Pietilainen

Helsinki University Central Hospital

Helsingin Yliopisto

S. Soderlund

Helsingin Yliopisto

Niina Matikainen

Helsinki University Central Hospital

Helsingin Yliopisto

Marcus Ståhlman

Göteborgs universitet

Per Olof Bergh

Göteborgs universitet

Martin Adiels

Göteborgs universitet

B. D. Piening

Stanford University

Marit Granér

Helsingin Yliopisto

N. Lundbom

Helsinki University Central Hospital

Kevin J. Williams

Göteborgs universitet

S. Romeo

Göteborgs universitet

Jens B Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

M. Snyder

Stanford University

Mathias Uhlen

Kungliga Tekniska Högskolan (KTH)

Göran Bergström

Göteborgs universitet

Rosie Perkins

Göteborgs universitet

H. U. Marschall

Göteborgs universitet

Fredrik Bäckhed

Göteborgs universitet

Marja Riitta Taskinen

Helsingin Yliopisto

Jan Borén

Göteborgs universitet

Cell Metabolism

1550-4131 (ISSN)

Vol. 27 3 559-571.e5

Ämneskategorier

Annan klinisk medicin

Livsmedelsvetenskap

Näringslära

DOI

10.1016/j.cmet.2018.01.005

Mer information

Senast uppdaterat

2019-01-17