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High fat diet impairs the function of glucagon-like peptide-1 producing L-cells.
- Source :
-
Peptides . Mar2016, Vol. 77, p21-27. 7p. - Publication Year :
- 2016
-
Abstract
- 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 , 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 signaling, which could impact on insulin secretion and satiety. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01969781
- Volume :
- 77
- Database :
- Academic Search Index
- Journal :
- Peptides
- Publication Type :
- Academic Journal
- Accession number :
- 113408235
- Full Text :
- https://doi.org/10.1016/j.peptides.2015.06.006