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

  1. Tooru M. Mizuno
  1. From the Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada
  1. Corresponding author: Tooru M. Mizuno, mizunot{at}cc.umanitoba.ca

Abstract

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.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 4 November 2008.

    A.L. and E.R.K. contributed equally to this study.

    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.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Received February 21, 2008.
    • Accepted October 20, 2008.
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  1. Diabetes vol. 58 no. 1 87-94
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