Norepinephrine controls both torpor initiation and emergence via distinct mechanisms in the mouse.
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 beta-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 T(b) 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 beta(3) adrenergic receptor antagonist to control mice during a torpor bout. Hence, NE signaling via beta(3) adrenergic receptors presumably in brown fat is the first neurotransmitter-receptor system identified that is required for normal recovery from torpor.
Swoap
Steven J
SJ
Department of Biology, Williams College, Williamstown, Massachusetts, United States of America. sswoap@williams.edu
Weinshenker
David
D
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000502:physiology; D058673:Adrenergic beta-3 Receptor Antagonists; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D004435:Eating / Q000235:genetics / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005215:Fasting / Q000502:physiology; D005260:Female; D020738:Leptin / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D020127:Recovery of Function / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D058673:Adrenergic beta-3 Receptor Antagonists; D020738:Leptin; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine