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

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Mardinoglu , A , Wu , H , Bjornson , E , Zhang , C , Hakkarainen , A , Räsänen , S M , Lee , S , Mancina , R M , Bergentall , M , Pietiläinen , K H , Söderlund , S , Matikainen , N , Stahlman , M , Bergh , P-O , Adiels , M , Piening , B D , Graner , M , Lundbom , N , Williams , K J , Romeo , S , Nielsen , J , Snyder , M , Uhlen , M , Bergstrom , G , Perkins , R , Marschall , H-U , Backhed , F , Taskinen , M-R & Boren , J 2018 , ' An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans ' , Cell Metabolism , vol. 27 , no. 3 , pp. 559-+ . https://doi.org/10.1016/j.cmet.2018.01.005

Title: An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
Author: Mardinoglu, Adil; Wu, Hao; Bjornson, Elias; Zhang, Cheng; Hakkarainen, Antti; Räsänen, Sari M.; Lee, Sunjae; Mancina, Rosellina M.; Bergentall, Mattias; Pietiläinen, Kirsi H.; Söderlund, Sanni; Matikainen, Niina; Stahlman, Marcus; Bergh, Per-Olof; Adiels, Martin; Piening, Brian D.; Graner, Marit; Lundbom, Nina; Williams, Kevin J.; Romeo, Stefano; Nielsen, Jens; Snyder, Michael; Uhlen, Mathias; Bergstrom, Goran; Perkins, Rosie; Marschall, Hanns-Ulrich; Backhed, Fredrik; Taskinen, Marja-Riitta; Boren, Jan
Contributor: University of Helsinki, Clinicum
University of Helsinki, Diabetes and Obesity Research Program
University of Helsinki, HUS Abdominal Center
University of Helsinki, HUS Internal Medicine and Rehabilitation
University of Helsinki, Research Programs Unit
University of Helsinki, Department of Medicine
University of Helsinki, Clinicum
University of Helsinki, Clinicum
Date: 2018-03-06
Language: eng
Number of pages: 18
Belongs to series: Cell Metabolism
ISSN: 1550-4131
URI: http://hdl.handle.net/10138/233915
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 beta-hydroxybutyrate concentrations, reflecting increased mitochondrial beta-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.
Subject: NONALCOHOLIC FATTY LIVER
GROWTH-FACTOR 21
VERY-LOW-CARBOHYDRATE
INSULIN-RESISTANCE
WEIGHT-LOSS
LIPID-METABOLISM
GUT MICROBIOTA
PPAR-ALPHA
FOLATE-DEFICIENCY
GLUTATHIONE METABOLISM
1182 Biochemistry, cell and molecular biology
3121 General medicine, internal medicine and other clinical medicine
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