期刊
SCIENTIFIC REPORTS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-18259-0
关键词
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资金
- NIHR Cambridge Biomedical Research Centre
- Agence Nationale de la Recherche (ANR MicroObes)
- Agence Nationale de la Recherche (ANR FunMetaGen)
- MetaCardis [HEALTH-F4-2012-305312]
- Wellcome Trust [106262/Z/14/Z, 106 263/Z/14/Z]
- MRC Metabolic Diseases Unit [MRC MC UU 12012/3, MRC MC UU 12012/5]
- Full4Health [266 408]
- Medical Research Council [MC_UU_12012/5, MC_UU_12012/3] Funding Source: researchfish
- Wellcome Trust [106263/Z/14/Z] Funding Source: researchfish
- MRC [MC_UU_12012/5, MC_UU_12012/3] Funding Source: UKRI
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.
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