Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-05

AUTHORS

KEC Bouter, GJ Bakker, E. Levin, AV Hartstra, RS Kootte, SD Udayappan, S. Katiraei, L. Bahler, P. W. Gilijamse, V. Tremaroli, M. Stahlman, F. Holleman, N. A. W. van Riel, HJ Verberne, JA Romijn, GM Dallinga-Thie, MJ Serlie, MT Ackermans, EM Kemper, K. Willems van Dijk, F. Backhed, AK Groen, M. Nieuwdorp

ABSTRACT

BACKGROUND: Gut microbiota-derived short-chain fatty acids (SCFAs) have been associated with beneficial metabolic effects. However, the direct effect of oral butyrate on metabolic parameters in humans has never been studied. In this first in men pilot study, we thus treated both lean and metabolic syndrome male subjects with oral sodium butyrate and investigated the effect on metabolism. METHODS: Healthy lean males (n = 9) and metabolic syndrome males (n = 10) were treated with oral 4 g of sodium butyrate daily for 4 weeks. Before and after treatment, insulin sensitivity was determined by a two-step hyperinsulinemic euglycemic clamp using [6,6-2H2]-glucose. Brown adipose tissue (BAT) uptake of glucose was visualized using 18F-FDG PET-CT. Fecal SCFA and bile acid concentrations as well as microbiota composition were determined before and after treatment. RESULTS: Oral butyrate had no effect on plasma and fecal butyrate levels after treatment, but did alter other SCFAs in both plasma and feces. Moreover, only in healthy lean subjects a significant improvement was observed in both peripheral (median Rd: from 71 to 82 µmol/kg min, p < 0.05) and hepatic insulin sensitivity (EGP suppression from 75 to 82% p < 0.05). Although BAT activity was significantly higher at baseline in lean (SUVmax: 12.4 ± 1.8) compared with metabolic syndrome subjects (SUVmax: 0.3 ± 0.8, p < 0.01), no significant effect following butyrate treatment on BAT was observed in either group (SUVmax lean to 13.3 ± 2.4 versus metabolic syndrome subjects to 1.2 ± 4.1). CONCLUSIONS: Oral butyrate treatment beneficially affects glucose metabolism in lean but not metabolic syndrome subjects, presumably due to an altered SCFA handling in insulin-resistant subjects. Although preliminary, these first in men findings argue against oral butyrate supplementation as treatment for glucose regulation in human subjects with type 2 diabetes mellitus. More... »

PAGES

155

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41424-018-0025-4

DOI

http://dx.doi.org/10.1038/s41424-018-0025-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1104159918

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29799027


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463 https://www.grid.ac/institutes/grid.16872.3a schema:alternateName VU University Medical Center
464 schema:name Department of Internal Medicine, AMC, Amsterdam, The Netherlands
465 Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands
466 Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
467 ICAR, VU University Medical Center, Amsterdam, The Netherlands
468 Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
469 rdf:type schema:Organization
470 https://www.grid.ac/institutes/grid.5650.6 schema:alternateName Academic Medical Center
471 schema:name Department of Clinical Chemistry, Laboratory of Endocrinology, AMC, Amsterdam, The Netherlands
472 Department of Clinical Pharmacy, AMC, Amsterdam, The Netherlands
473 Department of Endocrinology, AMC, Amsterdam, The Netherlands
474 Department of Internal Medicine, AMC, Amsterdam, The Netherlands
475 Department of Laboratory Medicine, University of Groningen, UMCG, Groningen, The Netherlands
476 Department of Nuclear Medicine, AMC, Amsterdam, The Netherlands
477 Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
478 rdf:type schema:Organization
479 https://www.grid.ac/institutes/grid.8761.8 schema:alternateName University of Gothenburg
480 schema:name Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
481 rdf:type schema:Organization
 




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