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

Mardinoglu A, Wu H, Bjornson E, Zhang C, Hakkarainen A, Räsänen SM, Lee S, Mancina RM, Bergentall M, Pietiläinen KH, Söderlund S, Matikainen N, Ståhlman M, Bergh PO, Adiels M, Piening BD, Granér M, Lundbom N, Williams KJ, Romeo S, Nielsen J, Snyder M, Uhlén M, Bergström G, Perkins R, Marschall HU, Bäckhed F, Taskinen MR, Borén J

Cell Metabolism 27 (3) 559-571.e5 [2018-03-00; online 2018-03-00]

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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PubMed 29456073

DOI 10.1016/j.cmet.2018.01.005

Crossref 10.1016/j.cmet.2018.01.005