Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome

Laura Gillard 1 Lore Billiauws 1, 2 Bogdan Stan-Iuga 1 Lara Ribeiro 3, 1 Anne-Charlotte Jarry 1 Jean-Baptiste Cavin 1 Françoise Cluzeaud 1 Camille Mayeur 4 Muriel Thomas 4 Jean-Noël Freund 5 Jean-Marc Lacorte 6, 7, 8 Maude Le Gall 1 André Bado 1 Francisca Joly 1, 2, * Johanne Le Beyec 8, 1, 6, *
* Auteur correspondant
1 CRI - Centre de recherche sur l'Inflammation
2 Service de Gastroentérologie et d’Assistance nutritive [AP-HP Hôpital Beaujon]
3 Service de Chirurgie Générale et Digestive [Hôpital Bichat - Claude Bernard, Paris]
4 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé humaine
5 Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques
6 UP4 - Université Paris-Sorbonne
7 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition
8 Service de Biochimie Endocrinienne et Oncologique [CHU Pitié-Salpêtrière]
Abstract : Short bowel syndrome (SBS) patients developing hyperphagia have a better outcome. Gastrointestinal endocrine adaptations help to improve intestinal functions and food behaviour. We investigated neuroendocrine adaptations in SBS patients and rat models with jejuno-ileal (IR-JI) or jejuno-colonic (IR-JC) anastomosis with and without parenteral nutrition. Circulating levels of ghrelin, PYY, GLP-1, and GLP-2 were determined in SBS rat models and patients. Levels of mRNA for proglucagon, PYY and for hypothalamic neuropeptides were quantified by qRT-PCR in SBS rat models. Histology and immunostaining for Ki67, GLP-1 and PYY were performed in SBS rats. IR-JC rats, but not IR-JI, exhibited significantly higher crypt depths and number of Ki67-positive cells than sham. Fasting and/or postprandial plasma ghrelin and PYY concentrations were higher, or tend to be higher, in IR-JC rats and SBS-JC patients than in controls. Proglucagon and Pyy mRNA levels were significantly enhanced in IR-JC rats. Levels of mRNA coding hypothalamic orexigenic NPY and AgRP peptides were significantly higher in IR-JC than in sham rats. We demonstrate an increase of plasma ghrelin concentrations, major changes in hypothalamic neuropeptides levels and greater induction of PYY in SBS-JC rats and patients suggesting that jejuno-colonic continuity creates a peculiar environment promoting further gut-brain adaptations.
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Scientific Reports, Nature Publishing Group, 2016, Scientific Reports 6, Article number: 28345 (2016), [Epub ahead of print]. 〈10.1038/srep28345〉
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Soumis le : lundi 18 juillet 2016 - 17:14:29
Dernière modification le : vendredi 31 août 2018 - 09:24:04

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Laura Gillard, Lore Billiauws, Bogdan Stan-Iuga, Lara Ribeiro, Anne-Charlotte Jarry, et al.. Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome. Scientific Reports, Nature Publishing Group, 2016, Scientific Reports 6, Article number: 28345 (2016), [Epub ahead of print]. 〈10.1038/srep28345〉. 〈inserm-01346345〉

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