title: Dietary non-digestible carbohydrates promote L-cell differentiation in the proximal colon of rats.
abstract: One of the challenges in type 2 diabetes treatment is to ensure pancreas functionality with gut peptides such as glucagon-like peptide-1 (GLP-1). We have recently shown that the endogenous GLP-1 production is promoted by dietary non-digestible carbohydrates (oligofructose), the higher GLP-1 secretion could participate in the control of obesity and associated disorders. This experimental study was designed to highlight the mechanisms of endogenous increase of GLP-1 following non-digestible carbohydrate feeding. Male Wistar rats were fed a standard diet (70.4 g/100 g total carbohydrates; controls) or the same diet supplemented with oligofructose (10 g/100 g diet) for 4 weeks. GLP-1-producing L-cells of the colon were quantified by immunohistochemistry. GLP-1 was quantified by ELISA, and proglucagon, neurogenin 3 and NeuroD mRNA were measured in the colon by quantitative RT-PCR. The number of GLP-1-expressing cells was doubled in the proximal colon of oligofructose-treated rats, a phenomenon correlated with the increase in proglucagon mRNA and peptide content in the tissue. Moreover, oligofructose increased the number of enteroendocrine L-cells in the proximal colon by a mechanism involving up-regulation of two differentiation factors: neurogenin 3 and NeuroD. It is the first demonstration that nutrients fermented in the gut may promote L-cell differentiation in the proximal colon, a phenomenon contributing to a higher endogenous GLP-1 production. These results suggest a new mechanism by which dietary fibres may lower food intake and fat mass development.
authors: Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, PMNT 73/69, Université catholique de Louvain, Av E Mounier, Brussels, Belgium.
authors: Patrice D
authors: PD
authors: Cani
authors: Sophie
authors: S
authors: Hoste
authors: Yves
authors: Y
authors: Guiot
authors: Nathalie M
authors: NM
authors: Delzenne
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis; D001835:Body Weight / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D003106:Colon / Q000166:cytology* / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000378:metabolism; D004435:Eating / Q000502:physiology; D019858:Enteroendocrine Cells / Q000378:metabolism / Q000502:physiology*; D005285:Fermentation / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis*; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D009844:Oligosaccharides / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004040:Dietary Carbohydrates; D052216:Glucagon-Like Peptide 1; D009419:Nerve Tissue Proteins; D009844:Oligosaccharides; C498696:Neurog3 protein, rat; C120489:oligofructose; C093564:Neurogenic differentiation factor 1