Journal
PEPTIDES
Volume 77, Issue -, Pages 21-27Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2015.06.006
Keywords
GLP-1; Enteroendocrine; L-cell; High fat diet
Funding
- Wellcome Trust [WT088357/Z/09/Z, WT084210/Z/07/Z]
- MRC Metabolic Diseases Unit [MRC_MC_UU_12012/3]
- Full4Health (FP7) [266408]
- MRC [MC_UU_12012/3, MC_UU_12012/5] Funding Source: UKRI
- Medical Research Council [MC_UU_12012/5, MC_UU_12012/5/B, MC_UU_12012/3] Funding Source: researchfish
- Wellcome Trust [106263/Z/14/Z] Funding Source: researchfish
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Glucagon-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 utilized 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: Two 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, MIxipl, 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 signaling, which could impact on insulin secretion and satiety. (C) 2015 The Authors. Published by Elsevier Inc.
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