title: High fat diet impairs the function of glucagon-like peptide-1 producing L-cells.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Richards
authors.affiliation: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Ramona
authors.initials: R
authors.lastname: Pais
authors.affiliation: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Abdella M
authors.initials: AM
authors.lastname: Habib
authors.affiliation: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Brighton
authors.affiliation: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Giles S H
authors.initials: GS
authors.lastname: Yeo
authors.affiliation: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address: fr222@cam.ac.uk.
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
authors.affiliation: Metabolic Research Laboratories and MRC Metabolic Diseases Unit, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address: fmg23@cam.ac.uk.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Gribble
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects*; D019858:Enteroendocrine Cells / Q000502:physiology*; D015870:Gene Expression; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D000090322:Homeobox Protein Nkx-2.2; D008297:Male; D008810:Mice, Inbred C57BL; D061251:Primary Cell Culture
chemical_list: D000090322:Homeobox Protein Nkx-2.2; C000715627:Nkx2-2 protein, mouse; D052216:Glucagon-Like Peptide 1
keywords: Enteroendocrine; GLP-1; High fat diet; L-cell