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

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2018 Feb 20

PMID 29456073

Citations 202

Authors

Adil Mardinoglu

Hao Wu

Elias Bjornson

Cheng Zhang

Antti Hakkarainen

Sari M Rasanen

Sunjae Lee

Rosellina M Mancina

Mattias Bergentall

Kirsi H Pietilainen

Sanni Soderlund

Niina Matikainen

Marcus Stahlman

Per-Olof Bergh

Martin Adiels

Brian D Piening

Marit Graner

Nina Lundbom

Kevin J Williams

Stefano Romeo

Jens Nielsen

Michael Snyder

Mathias Uhlen

Goran Bergstrom

Rosie Perkins

Hanns-Ulrich Marschall

Fredrik Backhed

Marja-Riitta Taskinen

Jan Boren

Affiliations

Soon will be listed here.

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.

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