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Aranias T, Grosfeld A, Poitou C, et al. Lipid-rich diet enhances L-cell density in obese subjects and in mice through improved L-cell differentiation. J Nutr Sci. 2015;4:e22doi: 10.1017/jns.2015.11.
Aranias, T., Grosfeld, A., Poitou, C., Omar, A. A., Le Gall, M., Miquel, S., Garbin, K., Ribeiro, A., Bouillot, J. L., Bado, A., Brot-Laroche, E., Clément, K., Leturque, A., Guilmeau, S., & Serradas, P. (2015). Lipid-rich diet enhances L-cell density in obese subjects and in mice through improved L-cell differentiation. Journal of nutritional science, 4e22. https://doi.org/10.1017/jns.2015.11
Aranias, Thomas, et al. "Lipid-rich diet enhances L-cell density in obese subjects and in mice through improved L-cell differentiation." Journal of nutritional science vol. 4 (2015): e22. doi: https://doi.org/10.1017/jns.2015.11
Aranias T, Grosfeld A, Poitou C, Omar AA, Le Gall M, Miquel S, Garbin K, Ribeiro A, Bouillot JL, Bado A, Brot-Laroche E, Clément K, Leturque A, Guilmeau S, Serradas P. Lipid-rich diet enhances L-cell density in obese subjects and in mice through improved L-cell differentiation. J Nutr Sci. 2015 May 20;4:e22. doi: 10.1017/jns.2015.11. eCollection 2015. PMID: 26157580; PMCID: PMC4459237.
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J Nutr Sci. 2015 May 20;4:e22. doi: 10.1017/jns.2015.11. eCollection 2015.

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

Journal of nutritional science

Thomas Aranias, Alexandra Grosfeld, Christine Poitou, Amal Ait Omar, Maude Le Gall, Sylvie Miquel, Kévin Garbin, Agnès Ribeiro, Jean-Luc Bouillot, André Bado, Edith Brot-Laroche, Karine Clément, Armelle Leturque, Sandra Guilmeau, Patricia Serradas

Affiliations

  1. Inserm UMR_S 1138 , Centre de Recherche des Cordeliers ; Sorbonne universités , UPMC Univ Paris 06 ; Sorbonne Cités , UPD Univ Paris 05 ; F-75006 , Paris , France.
  2. Inserm UMR_S 1138 , Centre de Recherche des Cordeliers ; Sorbonne universités , UPMC Univ Paris 06 ; Sorbonne Cités , UPD Univ Paris 05 ; F-75006 , Paris , France ; Institut de Cardiométabolisme et Nutrition , ICAN , Pitié-Salpêtrière Hospital , Paris , France.
  3. Institut de Cardiométabolisme et Nutrition , ICAN , Pitié-Salpêtrière Hospital , Paris , France ; Sorbonne universités , UPMC Univ Paris 06 , UMR_S ICAN U1166; Inserm; Nutriomic Team , F-75013 , Paris , France ; Assistance Publique-Hôpitaux de Paris , Pitié-Salpêtrière Hospital , Heart and Metabolism Department , Nutrition Unit , 47-83 Boulevard de l'Hôpital , 75651 Paris Cedex 13 , France.
  4. Inserm UMR_S 1138 , Centre de Recherche des Cordeliers ; Sorbonne universités , UPMC Univ Paris 06 ; Sorbonne Cités , UPD Univ Paris 05 ; F-75006 , Paris , France ; Inserm UMR_S 1149 , DHU Unity , UFR de Médecine Paris Diderot ; Sorbonne Cités , UPD Univ Paris 05 , F-75890 , Paris , France.
  5. INRA UMR 1319 Micalis , Interactions des Commensales et Probiotiques avec l'Hôte , F-78350 Jouy-en-Josas , France ; AgroParisTech , UMR 1319 Micalis , F-78350 Jouy-en-Josas , France.
  6. Assistance Publique-Hôpitaux de Paris , Surgery Department , Ambroise Paré Hospital , Boulogne-Billancourt , France.
  7. Inserm UMR_S 1149 , DHU Unity , UFR de Médecine Paris Diderot ; Sorbonne Cités , UPD Univ Paris 05 , F-75890 , Paris , France.
  8. Inserm UMR_S 1149 , DHU Unity , UFR de Médecine Paris Diderot ; Sorbonne Cités , UPD Univ Paris 05 , F-75890 , Paris , France ; Institut Cochin , Inserm UMR_S 1016 , CNRS UMR 8104 , Sorbonne Cités , UPD Univ Paris 05 ; Endocrinology , Metabolism and Diabetes Department , F-75014; Paris , France.

PMID: 26157580 PMCID: PMC4459237 DOI: 10.1017/jns.2015.11

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.

Keywords: BrdU, bromodeoxyuridine; CD, control diet; Enteroendocrine cells; GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide-1; Gut hormones; HFD, high-fat diet; High-fat diet; Intestine; PYY, peptide YY; foxa1, forkhead box protein A1; foxa2, forkhead box protein A2; isl1, insulin gene enhancer protein-1; ngn3, neurogenin3; pax6, paired box protein-6

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