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

作者：Mardinoglu Adil; Wu Hao; Bjornson Elias; Zhang Cheng; Hakkarainen Antti; Rasanen Sari M; Lee Sunjae; Mancina Rosellina M; Bergentall Mattias; Pietilainen Kirsi H; Soderlund 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

来源：Cell Metabolism, 2018, 27(3): 559-+.

DOI：10.1016/j.cmet.2018.01.005

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.

• 出版日期2018-3-6