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dc.contributor.authorRichards, Paulen
dc.contributor.authorPais, Ramonaen
dc.contributor.authorHabib, Abdella Men
dc.contributor.authorBrighton, Cheryl Aen
dc.contributor.authorYeo, Gilesen
dc.contributor.authorReimann, Franken
dc.contributor.authorGribble, Fionaen
dc.date.accessioned2015-07-21T14:35:51Z
dc.date.available2015-07-21T14:35:51Z
dc.date.issued2015-07-03en
dc.identifier.citationRichards et al. Peptides (2015) Vol. 77, pp. 21–27. DOI: 10.1016/j.peptides.2015.06.006en
dc.identifier.issn0196-9781
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/249001
dc.description.abstractGlucagon-like peptide-1 (GLP-1) acts as a satiety signal and enhances insulin release. This study examined how GLP-1 production from intestinal L-cells is modified by dietary changes. Methods: Transgenic mouse models were utilised in which L-cells could be purified by cell specific expression of a yellow fluorescent protein, Venus. Mice were fed on chow or 60% high fat diet (HFD) for 2 or 16 weeks. L-cells were purified by flow cytometry and analysed by microarray and quantitative RT-PCR. Enteroendocrine cell populations were examined by FACS analysis, and GLP-1 secretion was assessed in primary intestinal cultures. Results: 2 weeks HFD reduced the numbers of GLP-1 positive cells in the colon, and of GIP positive cells in the small intestine. Purified small intestinal L-cells showed major shifts in their gene expression profiles. In mice on HFD for 16 weeks, significant reductions were observed in the expression of L-cell specific genes, including those encoding gut hormones (Gip, Cck, Sct, Nts), prohormone processing enzymes (Pcsk1, Cpe), granins (Chgb, Scg2), nutrient sensing machinery (Slc5a1, Slc15a1, Abcc8, Gpr120) and enteroendocrine-specific transcription factors (Etv1, Isl1, Mlxipl, Nkx2.2 and Rfx6). A corresponding reduction in the GLP-1 secretory responsiveness to nutrient stimuli was observed in primary small intestinal cultures. Conclusion: Mice fed on HFD exhibited reduced expression in L-cells of many L-cell specific genes, suggesting an impairment of enteroendocrine cell function. Our results suggest that a western style diet may detrimentally affect the secretion of gut hormones and normal post-prandial signalling, which could impact on insulin secretion and satiety.
dc.description.sponsorshipThis work was funded by grants from the Wellcome Trust (WT088357/Z/09/Z and WT084210/Z/07/Z), the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/3) and Full4Health (FP7/2011-2015, grant agreement n° 266408). GLP-1 immuno-assays were performed by Keith Burling at the MRC-MDU.
dc.languageEnglishen
dc.language.isoenen
dc.publisherElsevier
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.subjectGLP-1en
dc.subjectEnteroendocrineen
dc.subjectL-cellen
dc.subjectHigh fat dieten
dc.titleHigh Fat Diet impairs the function of Glucagon-like Peptide-1 producing L-cellsen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.peptides.2015.06.006en
prism.endingPage27
prism.publicationDate2015en
prism.publicationNamePeptidesen
prism.startingPage21
prism.volume77en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderMRC
dc.rioxxterms.funderEU FP7
dc.rioxxterms.projectidWT088357/Z/09/Z
dc.rioxxterms.projectidWT084210/Z/07/Z
dc.rioxxterms.projectid266408
dcterms.dateAccepted2015-06-22en
rioxxterms.versionofrecord10.1016/j.peptides.2015.06.006en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-07-03en
dc.contributor.orcidYeo, Giles [0000-0001-8823-3615]
dc.contributor.orcidReimann, Frank [0000-0001-9399-6377]
dc.contributor.orcidGribble, Fiona [0000-0002-4232-2898]
dc.identifier.eissn1873-5169
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12012/5)
pubs.funder-project-idMRC (MC_UU_12012/3)
pubs.funder-project-idMedical Research Council (MC_UU_12012/5/B)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales