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) All Versions of this Article: 287/1/E105    most recent 00446.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Holder, J. L. Articles by Zinn, A. R. Search for Related Content PubMed PubMed Citation Articles by Holder, J. L., Jr Articles by Zinn, A. R.

Sim1 gene dosage modulates the homeostatic feeding response to increased dietary fat in mice

¹McDermott Center for Human Growth and Development and Department of Internal Medicine, ²Department of Psychiatry, and ³Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390; and ⁴Academia Sinica, Taipei, Taiwan

Submitted 2 October 2003 ; accepted in final form 18 February 2004

Haploinsufficiency of the transcription factor gene Sim1 has been previously implicated in hyperphagic obesity in humans and mice. To investigate the relation between Sim1 dosage and hyperphagia, we generated sim1-knockout mice and studied their growth and feeding behavior. Heterozygous mice weaned on standard chow consumed 14% more food per day than controls and developed obesity, hyperinsulinemia, and hyperleptinemia. The sim1 heterozygous mice were also significantly longer than controls. Heterozygous animals had modestly increased feeding efficiency, suggesting reduced energy expenditure, but voluntary wheel-running activity did not differ significantly between the two groups. We studied the effect of dietary fat on the feeding behavior of heterozygous sim1 mutant mice. The tempo and severity of weight gain were much greater in animals weaned on a high-fat diet. When acutely challenged with increased dietary fat, sim1 heterozygous mice weaned on the chow diet markedly increased their food consumption and caloric intake, whereas control mice reduced the mass of food they consumed and maintained approximately isocaloric intake. In wild-type adult mice, we detected Sim1 expression in the paraventricular and supraoptic nuclei, as previously reported in neonates, as well as in the amygdala and lateral hypothalamus, all regions implicated in feeding behavior. Our results indicate that Sim1 gene dosage modulates the homeostatic feeding response to increased dietary fat and likely plays a physiological role in the regulation of energy balance.

hypothalamus; transcription factor; feeding behavior

This article has been cited by other articles:

				M. Traurig, J. Mack, R. L. Hanson, M. Ghoussaini, D. Meyre, W. C. Knowler, S. Kobes, P. Froguel, C. Bogardus, and L. J. Baier Common Variation in SIM1 Is Reproducibly Associated With BMI in Pi ma Indians Diabetes, July 1, 2009; 58(7): 1682 - 1689. [Abstract] [Full Text] [PDF]

				C. Yang, D. Gagnon, P. Vachon, A. Tremblay, E. Levy, B. Massie, and J. L. Michaud Adenoviral-mediated modulation of Sim1 expression in the paraventricular nucleus affects food intake. J. Neurosci., June 28, 2006; 26(26): 7116 - 7120. [Abstract] [Full Text] [PDF]