Norepinephrine Controls Both Torpor Initiation and Emergence via Distinct Mechanisms in the Mouse

• Type of Material: Article
• Authors: Steven J. Swoap, Williams College; David Weinshenker, Emory University
• Language: English
• Date: 2008-12-24
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2008 Swoap et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0004038
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 3
• Issue: 12
• Start Page: e4038
• End Page: e4038
• Grant/Funding Information: This work was supported by NIH grant R15 HL081101-01 (to SJS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics
• Research Categories: Biology, Genetics; Biology, Neuroscience

Abstract

Some mammals, including laboratory mice, enter torpor in response to food deprivation, and leptin can attenuate these bouts of torpor. We previously showed that dopamine β-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), do not reduce circulating leptin upon fasting nor do they enter torpor. To test whether the onset of torpor in mice during a fast requires a NE-mediated reduction in circulating leptin, double mutant mice deficient in both leptin (ob/ob) and DBH (DBL MUT) were generated. Upon fasting, control and ob/ob mice entered torpor as assessed by telemetric core Tb acquisition. While fasting failed to induce torpor in Dbh -/- mice, leptin deficiency bypassed the requirement for NE, as DBL MUT mice readily entered torpor upon fasting. These data indicate that sympathetic activation of white fat and suppression of leptin is required for the onset of torpor in the mouse. Emergence from torpor was severely retarded in DBL MUT mice, revealing a novel, leptin-independent role for NE in torpor recovery. This phenotype was mimicked by administration of a β3 adrenergic receptor antagonist to control mice during a torpor bout. Hence, NE signaling via β3 adrenergic receptors presumably in brown fat is the first neurotransmitter-receptor system identified that is required for normal recovery from torpor.