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Sci Rep. 2018 Jan 8;8(1):74. doi: 10.1038/s41598-017-18259-0.

SCFAs strongly stimulate PYY production in human enteroendocrine cells.

Author information

1
University of Cambridge, Metabolic Research Laboratories and MRC Metabolic Diseases Unit, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. pl418@medschl.cam.ac.uk.
2
Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
3
Sorbonne Universités, UPMC Univ Paris 06, IFD, 4 place Jussieu, 75252, Paris, cedex 05, France.
4
US 1367 MetaGenoPolis, INRA, Université Paris-Saclay, 78350, Jouy en Josas, France.
5
University of Cambridge, Metabolic Research Laboratories and MRC Metabolic Diseases Unit, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

Abstract

Peptide-YY (PYY) and Glucagon-Like Peptide-1 (GLP-1) play important roles in the regulation of food intake and insulin secretion, and are of translational interest in the field of obesity and diabetes. PYY production is highest in enteroendocrine cells located in the distal intestine, mirroring the sites where high concentrations of short chain fatty acids (SCFAs) are produced by gut microbiota. We show here that propionate and butyrate strongly increased expression of PYY but not GCG in human cell line and intestinal primary culture models. The effect was predominantly attributable to the histone deacetylase inhibitory activity of SCFA and minor, but significant contributions of FFA2 (GPR43). Consistent with the SCFA-dependent elevation of PYY gene expression, we also observed increased basal and stimulated PYY hormone secretion. Interestingly, the transcriptional stimulation of PYY was specific to human-derived cell models and not reproduced in murine primary cultures. This is likely due to substantial differences in PYY gene structure between mouse and human. In summary, this study revealed a strong regulation of PYY production by SCFA that was evident in humans but not mice, and suggests that high fibre diets elevate plasma concentrations of the anorexigenic hormone PYY, both by targeting gene expression and hormone secretion.

PMID:
29311617
PMCID:
PMC5758799
DOI:
10.1038/s41598-017-18259-0
[Indexed for MEDLINE]
Free PMC Article

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