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) 19327420 (eISSN)
Vol. 27 3 559-571.e5Ämneskategorier
Annan klinisk medicin
Livsmedelsvetenskap
Näringslära
DOI
10.1016/j.cmet.2018.01.005