HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nonogaki, K. Articles by Tecott, L. H. Search for Related Content PubMed PubMed Citation Articles by Nonogaki, K. Articles by Tecott, L. H. Social Bookmarking                What's this?

Hyperactivity and Reduced Energy Cost of Physical Activity in Serotonin 5-HT_2C Receptor Mutant Mice

¹ From the Department of Psychiatry and Center for Neurobiology and Psychiatry, University of California, San Francisco, San Francisco, California

We have observed late-onset obesity in mutant mice lacking the serotonin 5-HT_2C receptor. Despite chronically elevated food intake, young adult mutants exhibit neither elevated adiposity nor altered glucose or fat homeostasis. However, obesity subsequently develops after 6 months of age without increases in their level of hyperphagia. In this study, we investigated determinants of energy expenditure in 5-HT_2C receptor mutant mice. Young adult mutants displayed patterns of elevated activity levels that were enhanced by fasting and tightly associated with repeated visits to a food source. Surprisingly, subsequent obesity development occurred despite persisting locomotor hyperactivity and without age-related declines in resting metabolic rate. Rather, substantial reductions in the energy cost of locomotor activity (LA) were observed in 5-HT_2C receptor mutant mice. Moreover, both mutant and wild-type mice displayed age-related declines in the energy cost of LA, indicating that this process may be regulated by both aging and serotonergic signaling. These results indicate that a mutation of the 5-HT_2C receptor gene (htr2c) increases LA, which contributes to the maintenance of normal body composition in young adult mutants despite their hyperphagia. Moreover, age-dependent reductions in the energy cost of physical activity could contribute to the subsequent development of late-onset obesity in 5-HT_2C receptor mutant mice.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				A. S. Garfield and L. K. Heisler Pharmacological targeting of the serotonergic system for the treatment of obesity J. Physiol., January 1, 2009; 587(1): 49 - 60. [Abstract] [Full Text] [PDF]

				Y. Kawahara, A. Grimberg, S. Teegarden, C. Mombereau, S. Liu, T. L. Bale, J. A. Blendy, and K. Nishikura Dysregulated Editing of Serotonin 2C Receptor mRNAs Results in Energy Dissipation and Loss of Fat Mass J. Neurosci., November 26, 2008; 28(48): 12834 - 12844. [Abstract] [Full Text] [PDF]

				K. Nonogaki, K. Nozue, and Y. Oka Social Isolation Affects the Development of Obesity and Type 2 Diabetes in Mice Endocrinology, October 1, 2007; 148(10): 4658 - 4666. [Abstract] [Full Text] [PDF]

				E. L. Sullivan, F. H. Koegler, and J. L. Cameron Individual differences in physical activity are closely associated with changes in body weight in adult female rhesus monkeys (Macaca mulatta) Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2006; 291(3): R633 - R642. [Abstract] [Full Text] [PDF]

				K. A. Graham, D. O. Perkins, L. J. Edwards, R. C. Barrier Jr., J. A. Lieberman, and J. B. Harp Effect of Olanzapine on Body Composition and Energy Expenditure in Adults With First-Episode Psychosis Am J Psychiatry, January 1, 2005; 162(1): 118 - 123. [Abstract] [Full Text] [PDF]

				L. H. Tecott The Genes and Brains of Mice and Men Am J Psychiatry, April 1, 2003; 160(4): 646 - 656. [Abstract] [Full Text] [PDF]