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Roles of xenin in the regulation of energy balance: central nervous system control of food intake and body weight by xenin

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dc.contributor.supervisor Mizuno, Tooru (Physiology) en_US
dc.contributor.author Kim, Eun Ran
dc.date.accessioned 2011-12-21T18:39:37Z
dc.date.available 2011-12-21T18:39:37Z
dc.date.issued 2010-08-30
dc.identifier.citation Behav Brain Res. 2008 Dec 1;194(1):66-71. Epub 2008 Jul 1. en_US
dc.identifier.citation Neurosci Lett. 2010 Jan 1;468(1):64-7. Epub 2009 Oct 24. en_US
dc.identifier.citation Neurosci Lett. 2010 Aug 30;481(1):59-63. Epub 2010 Jun 25. en_US
dc.identifier.citation Diabetes. 2009 Jan;58(1):87-94. Epub 2008 Nov 4. en_US
dc.identifier.uri http://hdl.handle.net/1993/5006
dc.description.abstract Xenin, a gastrointestinal peptide, is structurally similar to neurotensin which functions as a satiety factor via neurotensin receptor 1 (Ntsr1). Metabolic effect of the adipocyte hormone leptin is partially mediated through the Ntsr1 and interleukin 1 type I receptor (IL-1RI) in the central nervous system (CNS). Xenin reduces food intake when administered centrally and peripherally. Apart from its acute feeding-suppressing effect, the distinct metabolic action of xenin and the mechanism of xenin-induced anorexia remain to be elucidated. We hypothesized that prolonged xenin treatment reduces food intake and body weight and increases energy expenditure. We also hypothesized that xenin reduces food intake by activating CNS signalling pathways including Ntsr1 and IL-1RI and by interacting with leptin. To address these hypotheses, we examined (1) the effect of xenin treatment on food intake, energy expenditure and body weight in wild-type, Ntsr1-deficient and IL-1RI-deficient mice, (2) the effect of xenin on hypothalamic Fos and interleukin 1β (IL-1β) expression in wild-type mice, and (3) the effect of co-injection of xenin and leptin on food intake and body weight in wild-type mice. Daily intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) xenin treatment (6-10 days) significantly reduced body weight gain and adiposity with a transient reduction in food intake in wild-type mice. Xenin treatment (i.p.) caused a significant reduction in respiratory quotient without changes in energy expenditure. Xenin treatment increased hormone sensitive lipase (HSL) mRNA levels and reduced acyl-coenzyme A: diacylglycerol acyltransferase 2 (DGAT2) mRNA levels in white adipose tissue. Xenin (i.p.) increased the number of Fos-immunoreactive cells in the hypothalamus and the brainstem and increased hypothalamic IL-1β mRNA levels. The anorectic effects of xenin and leptin were abolished or attenuated in mice lacking Ntsr1 or IL-1RI. I.p. co-administration of xenin and leptin caused greater reductions in food intake and body weight compared to leptin alone and xenin alone. These data suggest that long-term xenin treatment reduces body weight by reducing food intake and increasing fat oxidization. Xenin reduces food intake by activating CNS signalling pathways involving Ntsr1 and IL-1 possibly through the interaction with leptin. These findings implicate xenin and its downstream mediators as potential targets for anti-obesity drugs. en_US
dc.publisher Elsevier en_US
dc.publisher American diabetes association en_US
dc.subject xenin en_US
dc.subject metabolism en_US
dc.title Roles of xenin in the regulation of energy balance: central nervous system control of food intake and body weight by xenin en_US
dc.degree.discipline Physiology en_US
dc.contributor.examiningcommittee Pierce, Grant (Physiology) Shiu, Robert (Physiology) Bergen, Hugo ( Human anatomy and cell science) Havel, Peter J(University of California, Davis) en_US
dc.degree.level Doctor of Philosophy (Ph.D.) en_US
dc.description.note February 2012 en_US


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