High fat diet impairs the function of glucagon-like peptide-1 producing L-cells

Peptides. 2016 Mar:77:21-7. doi: 10.1016/j.peptides.2015.06.006. Epub 2015 Jul 3.

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.

Keywords: Enteroendocrine; GLP-1; High fat diet; L-cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Diet, High-Fat / adverse effects*
  • Enteroendocrine Cells / physiology*
  • Gene Expression
  • Glucagon-Like Peptide 1 / genetics
  • Glucagon-Like Peptide 1 / metabolism*
  • Homeobox Protein Nkx-2.2
  • Male
  • Mice, Inbred C57BL
  • Primary Cell Culture

Substances

  • Homeobox Protein Nkx-2.2
  • Nkx2-2 protein, mouse
  • Glucagon-Like Peptide 1