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An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
Open accessAbstract
SUMMARY 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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Self-citation
Metadata
- Authors
- 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., Ståhlman, M., Bergh, P.-O., Adiels, M., Piening, B. D., Granér, M., Lundbom, N., Williams, K. J., Romeo, S., Nielsen, J., Snyder, M., Uhlén, M., Bergström, G., Perkins, R., Marschall, H.-U., Bäckhed, F., Taskinen, M.-R., & Borén, J.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 27
- Issue
- 3
- Pages
- 559-571.e5
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2788488000
- Cited by
- 453
- References
- 23
- FWCI
- 32.22
- Type
- journal article
- Language
- en
- Open access
- bronze
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