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Lipid-rich diet enhances L-cell density in obese subjects and in mice through improved L-cell differentiation

  • Thomas Aranias (a1), Alexandra Grosfeld (a1) (a2), Christine Poitou (a2) (a3) (a4), Amal Ait Omar (a1), Maude Le Gall (a1) (a5), Sylvie Miquel (a6) (a7), Kévin Garbin (a1), Agnès Ribeiro (a1) (a2), Jean-Luc Bouillot (a8), André Bado (a5), Edith Brot-Laroche (a1) (a2), Karine Clément (a2) (a3) (a4), Armelle Leturque (a1) (a2), Sandra Guilmeau (a5) (a9) and Patricia Serradas (a1) (a2)...
Abstract

The enterohormone glucagon-like peptide-1 (GLP-1) is required to amplify glucose-induced insulin secretion that facilitates peripheral glucose utilisation. Alteration in GLP-1 secretion during obesity has been reported but is still controversial. Due to the high adaptability of intestinal cells to environmental changes, we hypothesised that the density of GLP-1-producing cells could be modified by nutritional factors to prevent the deterioration of metabolic condition in obesity. We quantified L-cell density in jejunum samples collected during Roux-en-Y gastric bypass in forty-nine severely obese subjects analysed according to their fat consumption. In mice, we deciphered the mechanisms by which a high-fat diet (HFD) makes an impact on enteroendocrine cell density and function. L-cell density in the jejunum was higher in obese subjects consuming >30 % fat compared with low fat eaters. Mice fed a HFD for 8 weeks displayed an increase in GLP-1-positive cells in the jejunum and colon accordingly to GLP-1 secretion. The regulation by the HFD appears specific to GLP-1-producing cells, as the number of PYY (peptide YY)-positive cells remained unchanged. Moreover, genetically obese ob/ob mice did not show alteration of GLP-1-positive cell density in the jejunum or colon, suggesting that obesity per se is not sufficient to trigger the mechanism. The higher L-cell density in HFD-fed mice involved a rise in L-cell terminal differentiation as witnessed by the increased expression of transcription factors downstream of neurogenin3 (Ngn3). We suggest that the observed increase in GLP-1-positive cell density triggered by high fat consumption in humans and mice might favour insulin secretion and therefore constitute an adaptive response of the intestine to balance diet-induced insulin resistance.

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Copyright
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
* Corresponding author: Dr Alexandra Grosfeld, fax +33 143251615, email alexandra.grosfeld@crc.jussieu.fr
References
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