The preproghrelin gene is required for the normal integration of thermoregulation and sleep in mice
- aSleep and Performance Research Center, Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WA 99164;
- bDepartment of Biological Sciences, Fordham University, Bronx, NY 10458; and
- cHuffington Center on Aging, Departments of Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, TX 77030
Abstract
Peptidergic mechanisms controlling feeding, metabolism, thermoregulation, and sleep overlap in the hypothalamus. Low ambient temperatures and food restriction induce hypothermic (torpor) bouts and characteristic metabolic and sleep changes in mice. We report that mice lacking the preproghrelin gene, but not those lacking the ghrelin receptor, have impaired abilities to manifest and integrate normal sleep and thermoregulatory responses to metabolic challenges. In response to fasting at 17 °C (a subthermoneutral ambient temperature), preproghrelin knockout mice enter hypothermic bouts associated with reduced sleep, culminating in a marked drop in body temperature to near-ambient levels. Prior treatment with obestatin, another preproghrelin gene product, attenuates the hypothermic response of preproghrelin knockout mice. Results suggest that obestatin is a component in the coordinated regulation of metabolism and sleep during torpor.
Footnotes
- 1To whom correspondence should be addressed at the present address: WWAMI Medical Education Program, Washington State University, Spokane, WA 99210. E-mail: eszentirmai{at}wsu.edu
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Edited by Charles A. Dinarello, University of Colorado Health Sciences Center, Denver, CO, and approved June 11, 2009
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Author contributions: É.S., L.K., and J.M.K. designed research; É.S., Y.S., and R.G.S. performed research; É.S. and L.K. analyzed data; and É.S., L.K., Y.S., R.G.S., and J.M.K. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0903090106/DCSupplemental.
