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Xenin, a Gastrointestinal Peptide, Regulates Feeding Independent of the Melanocortin Signaling Pathway

OBJECTIVE—Xenin, a 25–amino acid peptide, was initially isolated from human gastric mucosa. Plasma levels of xenin rise after a meal in humans, and administration of xenin inhibits feeding in rats and chicks. However, little is known about the mechanism by which xenin regulates food intake. Signalin...

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Autores principales: Leckstrom, Arnold, Kim, Eun Ran, Wong, Davie, Mizuno, Tooru M.
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606897/
https://www.ncbi.nlm.nih.gov/pubmed/18984739
http://dx.doi.org/10.2337/db08-0260
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author Leckstrom, Arnold
Kim, Eun Ran
Wong, Davie
Mizuno, Tooru M.
author_facet Leckstrom, Arnold
Kim, Eun Ran
Wong, Davie
Mizuno, Tooru M.
author_sort Leckstrom, Arnold
collection PubMed
description OBJECTIVE—Xenin, a 25–amino acid peptide, was initially isolated from human gastric mucosa. Plasma levels of xenin rise after a meal in humans, and administration of xenin inhibits feeding in rats and chicks. However, little is known about the mechanism by which xenin regulates food intake. Signaling pathways including leptin and melanocortins play a pivotal role in the regulation of energy balance. Therefore, we addressed the hypothesis that xenin functions as a satiety factor by acting through the melanocortin system or by interacting with leptin. RESEARCH DESIGN AND METHODS—The effect of intracerebroventricular and intraperitoneal administration of xenin on food intake was examined in wild-type, agouti, and ob/ob mice. The effect of intracerebroventricular injection of SHU9119, a melanocortin receptor antagonist, on xenin-induced anorexia was also examined in wild-type mice. To determine whether the hypothalamus mediates the anorectic effect of xenin, we examined the effect of intraperitoneal xenin on hypothalamic Fos expression. RESULTS—Both intracerebroventricular and intraperitoneal administration of xenin inhibited fasting-induced hyperphagia in wild-type mice in a dose-dependent manner. The intraperitoneal injection of xenin also reduced nocturnal intake in ad libitum–fed wild-type mice. The intraperitoneal injection of xenin increased Fos immunoreactivity in hypothalamic nuclei, including the paraventricular nucleus and the arcuate nucleus. Xenin reduced food intake in agouti and ob/ob mice. SHU9119 did not block xenin-induced anorexia. CONCLUSIONS—Our data suggest that xenin reduces food intake partly by acting through the hypothalamus but via signaling pathways that are independent of those used by leptin or melanocortins.
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spelling pubmed-26068972010-01-01 Xenin, a Gastrointestinal Peptide, Regulates Feeding Independent of the Melanocortin Signaling Pathway Leckstrom, Arnold Kim, Eun Ran Wong, Davie Mizuno, Tooru M. Diabetes Metabolism OBJECTIVE—Xenin, a 25–amino acid peptide, was initially isolated from human gastric mucosa. Plasma levels of xenin rise after a meal in humans, and administration of xenin inhibits feeding in rats and chicks. However, little is known about the mechanism by which xenin regulates food intake. Signaling pathways including leptin and melanocortins play a pivotal role in the regulation of energy balance. Therefore, we addressed the hypothesis that xenin functions as a satiety factor by acting through the melanocortin system or by interacting with leptin. RESEARCH DESIGN AND METHODS—The effect of intracerebroventricular and intraperitoneal administration of xenin on food intake was examined in wild-type, agouti, and ob/ob mice. The effect of intracerebroventricular injection of SHU9119, a melanocortin receptor antagonist, on xenin-induced anorexia was also examined in wild-type mice. To determine whether the hypothalamus mediates the anorectic effect of xenin, we examined the effect of intraperitoneal xenin on hypothalamic Fos expression. RESULTS—Both intracerebroventricular and intraperitoneal administration of xenin inhibited fasting-induced hyperphagia in wild-type mice in a dose-dependent manner. The intraperitoneal injection of xenin also reduced nocturnal intake in ad libitum–fed wild-type mice. The intraperitoneal injection of xenin increased Fos immunoreactivity in hypothalamic nuclei, including the paraventricular nucleus and the arcuate nucleus. Xenin reduced food intake in agouti and ob/ob mice. SHU9119 did not block xenin-induced anorexia. CONCLUSIONS—Our data suggest that xenin reduces food intake partly by acting through the hypothalamus but via signaling pathways that are independent of those used by leptin or melanocortins. American Diabetes Association 2009-01 /pmc/articles/PMC2606897/ /pubmed/18984739 http://dx.doi.org/10.2337/db08-0260 Text en Copyright © 2009, American Diabetes Association Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Metabolism
Leckstrom, Arnold
Kim, Eun Ran
Wong, Davie
Mizuno, Tooru M.
Xenin, a Gastrointestinal Peptide, Regulates Feeding Independent of the Melanocortin Signaling Pathway
title Xenin, a Gastrointestinal Peptide, Regulates Feeding Independent of the Melanocortin Signaling Pathway
title_full Xenin, a Gastrointestinal Peptide, Regulates Feeding Independent of the Melanocortin Signaling Pathway
title_fullStr Xenin, a Gastrointestinal Peptide, Regulates Feeding Independent of the Melanocortin Signaling Pathway
title_full_unstemmed Xenin, a Gastrointestinal Peptide, Regulates Feeding Independent of the Melanocortin Signaling Pathway
title_short Xenin, a Gastrointestinal Peptide, Regulates Feeding Independent of the Melanocortin Signaling Pathway
title_sort xenin, a gastrointestinal peptide, regulates feeding independent of the melanocortin signaling pathway
topic Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606897/
https://www.ncbi.nlm.nih.gov/pubmed/18984739
http://dx.doi.org/10.2337/db08-0260
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