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

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.

• Authors: Laura Gillard, Lore Billiauws, Bogdan Stan-Iuga, Lara Ribeiro-Parenti, Anne-Charlotte Jarry, Jean-Baptiste Cavin, Françoise Cluzeaud, Camille Mayeur, Muriel Thomas, Jean-Noël Freund, Jean-Marc Lacorte, Maude Le Gall, André Bado, Francisca Joly, Johanne Le Beyec
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 28345 (06 21 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27323884 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Agouti-Related Protein
• Ghrelin
• Glucagon-Like Peptide 2
• Ki-67 Antigen
• Neuropeptide Y
• RNA, Messenger
• Peptide YY
• Proglucagon
• Glucagon-Like Peptide 1

Topics

• Adult
• Aged
• Agouti-Related Protein (metabolism)
• Anastomosis, Surgical
• Animals
• Colon (pathology)
• Disease Models, Animal
• Feeding Behavior
• Female
• Ghrelin (blood)
• Glucagon-Like Peptide 1 (blood)
• Glucagon-Like Peptide 2 (blood)
• Humans
• Hyperphagia (metabolism)
• Hypothalamus (metabolism)
• Intestinal Mucosa (metabolism)
• Jejunum (pathology)
• Ki-67 Antigen (metabolism)
• Male
• Middle Aged
• Neuropeptide Y (metabolism)
• Peptide YY (blood)
• Proglucagon (metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Real-Time Polymerase Chain Reaction
• Short Bowel Syndrome (metabolism)