期刊
INTERNATIONAL JOURNAL OF OBESITY
卷 39, 期 3, 页码 424-429出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ijo.2014.153
关键词
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资金
- MRC
- BBSRC
- NIHR
- Integrative Mammalian Biology (IMB) Capacity Building Award
- EuroCHIP grant [FP7-HEALTH-2009-241592]
- NIHR Imperial Biomedical Research Centre Funding Scheme
- BBSRC DRINC [BB/H014039/1]
- BBSRC studentship
- BBSRC [BB/E52708X/1, BB/H004971/1, BB/I00842X/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/I00842X/1, BB/H004971/1, BB/E52708X/1, BB/L004259/1, 1527476] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0507-10337, CDF-2011-04-006, NF-SI-0513-10080] Funding Source: researchfish
- National Institutes of Health Research (NIHR) [CDF-2011-04-006] Funding Source: National Institutes of Health Research (NIHR)
BACKGROUND AND OBJECTIVES: The gut hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) acutely suppress appetite. The short chain fatty acid (SCFA) receptor, free fatty acid receptor 2 (FFA2) is present on colonic enteroendocrine L cells, and a role has been suggested for SCFAs in appetite regulation. Here, we characterise the in vitro and in vivo effects of colonic propionate on PYY and GLP-1 release in rodents, and investigate the role of FFA2 in mediating these effects using FFA2 knockout mice. METHODS: We used Wistar rats, C57BL6 mice and free fatty acid receptor 2 knockout (FFA(-/-)) mice on a C57BL6 background to explore the impact of the SCFA propionate on PYY and GLP-1 release. Isolated colonic crypt cultures were used to assess the effects of propionate on gut hormone release in vitro. We subsequently developed an in vivo technique to assess gut hormone release into the portal vein following colonic infusion of propionate. RESULTS: Propionate stimulated the secretion of both PYY and GLP-1 from wild-type primary murine colonic crypt cultures. This effect was significantly attenuated in cultures from FFA2(-/-) mice. Intra-colonic infusion of propionate elevated PYY and GLP-1 levels in jugular vein plasma in rats and in portal vein plasma in both rats and mice. However, propionate did not significantly stimulate gut hormone release in FFA2(-/-) mice. CONCLUSIONS: Intra-colonic administration of propionate stimulates the concurrent release of both GLP-1 and PYY in rats and mice. These data demonstrate that FFA2 deficiency impairs SCFA-induced gut hormone secretion both in vitro and in vivo.
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