An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans.
FGF21; NAFLD; PPAR-α; Streptococcus; carbohydrate-restricted diet; folate; inflammation; microbiome; multi-omics; β-oxidation
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, 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; Ståhlman, Marcus; Bergh, Per-Olof; Adiels, Martin; Piening, Brian D.; Granér, Marit; Lundbom, Nina; Williams, Kevin J; Romeo, Stefano; Nielsen, Jens; Snyder, Michael; Uhlén, Mathias; Bergström, Göran; Perkins, Rosie; Marschall, Hanns-Ulrich; Bäckhed, Fredrik; Taskinen, Marja-Riitta; and Borén, Jan, "An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans." (2018). Articles, Abstracts, and Reports. 1024.