Tooru Mizuno

University of Manitoba, Canada

Abstract

[O05] Regulation of food intake by xenin

The central nervous system (CNS) plays an important role in the regulation of energy balance by integrating a variety of humoral, hormonal, and neural signals.  Included among these are hormones which are synthesized and secreted by the gastrointestinal tract.  Xenin is a 25-amino acid peptide that was initially identified in human gastric mucosa.  Xenin is structurally similar to neurotensin which functions as a satiety factor and binds to neurotensin receptor 1 (Ntsr1) with an affinity comparable to that of neurotensin.  Neurotensin-induced anorexia is mediated through the Ntsr1, while the specific receptors for xenin have not yet been identified.  Similar to other anorectic gastrointestinal peptides, levels of circulating xenin increase after a meal, and intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of xenin reduces food intake in rats and chicks.  These findings suggest that xenin may also regulate food intake by acting as a satiety factor.  However, little is known about the mechanisms by which xenin regulates food intake.  Furthermore, whether xenin plays a role in the regulation of energy expenditure and body weight remains unknown.  Based on similarities in structure and biological function (e.g. feeding suppression) between xenin and neurotensin, we hypothesized that xenin inhibits feeding, increases energy expenditure, and reduces body weight by acting through Ntsr1 in the CNS.  We found that (1) both i.p. and i.c.v. injections of xenin reduce food intake in lean and obese mice, (2) daily i.p. and i.c.v. injections of xenin reduce body weight gain in lean and obese mice, (3) the feeding-suppressing effect of xenin is mediated by Ntsr1, but not by the melanocortin system, and (4) the i.p. xenin stimulates specific regions of the CNS.  These findings suggest that xenin regulates food intake through the activation of specific CNS pathways and that enhancement of xenin action is a potential strategy to ameliorate obesity.

Keywords: Gastrointestinal peptide; Central nervous system; Feeding; Obesity

Biography

I received my Ph.D. in Physiology at Yokohama City University School of Medicine in Japan in 1994.  Afterwards I went to Fishberg Center for Neurobiology at Mount Sinai School of Medicine in New York and Beth Israel Deaconess Medical Center at Harvard Medical School to receive post-doctoral training.  In 2004, I came to the University of Manitoba’s Department of Physiology as Assistant Professor and Canada Research Chair.  My research focuses on obesity and metabolic control.  More specifically, I study roles of neuropeptides and gastrointestinal peptides in the regulation of appetite and metabolism.