Enhanced Ghrelin Levels and Hypothalamic Orexigenic AgRP and NPY Neuropeptide Expression in Models of Jejuno-Colonic Short Bowel Syndrome.
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.
Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France.
Laura
L
Gillard
Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France.|AP-HP, Hôpital Beaujon, Service de Gastroentérologie et d'Assistance nutritive, Clichy, France.
Lore
L
Billiauws
Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France.
Bogdan
B
Stan-Iuga
Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France.|AP-HP, Hôpital Bichat - Claude Bernard, Service de Chirurgie Générale et Digestive, F-75018 Paris, France.
Lara
L
Ribeiro-Parenti
Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France.
Anne-Charlotte
AC
Jarry
Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France.
Jean-Baptiste
JB
Cavin
Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France.
Françoise
F
Cluzeaud
Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
Camille
C
Mayeur
Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
Muriel
M
Thomas
INSERM UMR_S1113, Université de Strasbourg, Faculté de Médecine, FMTS, 67081 Strasbourg, France.
Jean-Noël
JN
Freund
INSERM, UMR_S 1166, Research Institute of Cardiovascular Disease, Metabolism and Nutrition, ICAN, Université Pierre et Marie Curie, Sorbonne Université, F-75013, Paris, France.|AP-HP, Hôpital Pitié-Salpêtrière-Charles Foix, Biochimie Endocrinienne et Oncologique, F-75651, Paris, Cedex.|Université Pierre et Marie Curie, Sorbonne Université, F-75005, Paris, France.
Jean-Marc
JM
Lacorte
Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France.
Maude
M
Le Gall
Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France.
André
A
Bado
Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France.|AP-HP, Hôpital Beaujon, Service de Gastroentérologie et d'Assistance nutritive, Clichy, France.
Francisca
F
Joly
Inserm UMR1149, UFR de Médecine Paris Diderot, Université Paris Diderot, Sorbonne Paris Cité, DHU Unity, AP-HP, F-75890 Paris, France.|AP-HP, Hôpital Pitié-Salpêtrière-Charles Foix, Biochimie Endocrinienne et Oncologique, F-75651, Paris, Cedex.|Université Pierre et Marie Curie, Sorbonne Université, F-75005, Paris, France.
Johanne
J
Le Beyec
D000328:Adult; D000368:Aged; D054369:Agouti-Related Protein / Q000378:metabolism*; D000714:Anastomosis, Surgical; D000818:Animals; D003106:Colon / Q000473:pathology*; D004195:Disease Models, Animal; D005247:Feeding Behavior; D005260:Female; D054439:Ghrelin / Q000097:blood*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D053767:Glucagon-Like Peptide 2 / Q000097:blood; D006801:Humans; D006963:Hyperphagia / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000473:pathology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000378:metabolism*; D019894:Peptide YY / Q000097:blood; D052336:Proglucagon / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012778:Short Bowel Syndrome / Q000378:metabolism*
D054369:Agouti-Related Protein; D054439:Ghrelin; D053767:Glucagon-Like Peptide 2; D019394:Ki-67 Antigen; D009478:Neuropeptide Y; D012333:RNA, Messenger; D019894:Peptide YY; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1