High Fat Diet impairs the function of Glucagon-like Peptide-1 producing L-cells
Habib, Abdella M
Brighton, Cheryl A
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Richards, P., Pais, R., Habib, A. M., Brighton, C. A., Yeo, G., Reimann, F., & Gribble, F. (2015). High Fat Diet impairs the function of Glucagon-like Peptide-1 producing L-cells. Peptides, 77 21-27. https://doi.org/10.1016/j.peptides.2015.06.006
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 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.
GLP-1, Enteroendocrine, L-cell, High fat diet
This 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.
Medical Research Council (MC_UU_12012/5/B)
External DOI: https://doi.org/10.1016/j.peptides.2015.06.006
This record's URL: https://www.repository.cam.ac.uk/handle/1810/249001
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/