Full Papers

Dietary non-digestible carbohydrates promote L-cell differentiation in the proximal colon of rats

Patrice D. Cani^a1, Sophie Hoste^a1, Yves Guiot^a2 and Nathalie M. Delzenne^a1 c1

^a1 Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, PMNT 73/69, Université catholique de Louvain, Av. E. Mounier, 1200 Brussels, Belgium

^a2 Department of Pathology, Cliniques Universitaires St Luc, Avenue Hippocrate, 10 (box 1712), B-1200, Brussels, Belgium

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.

(Received August 28 2006)

(Revised November 29 2006)

(Accepted January 04 2007)

Key Words:

• L-cells;
• Neurogenin 3;
• NeuroD;
• Proglucagon;
• Carbohydrates

Correspondence:

^c1 *Corresponding author: Prof. Nathalie M. Delzenne, fax +32 2 764 73 59, email delzenne@pmnt.ucl.ac.be

Footnotes

Abbreviations: GLP-1, glucagon-like peptide-1; NGN3, neurogenin 3; OFS, oligofructose