SR59230A, a beta-3 adrenoceptor antagonist, inhibits ultradian brown adipose tissue thermogenesis and interrupts associated episodic brain and body heating

Am J Physiol Regul Integr Comp Physiol. 2011 Oct;301(4):R987-94. doi: 10.1152/ajpregu.00085.2011. Epub 2011 Aug 3.

Abstract

Brown adipose tissue (BAT) thermogenesis occurs episodically in an ultradian manner approximately every 80-100 min during the waking phase of the circadian cycle, together with highly correlated increases in brain and body temperatures, suggesting that BAT thermogenesis contributes to brain and body temperature increases. We investigated this in conscious Sprague-Dawley rats by determining whether inhibition of BAT thermogenesis via blockade of beta-3 adrenoceptors with SR59230A interrupts ultradian episodic increases in brain and body temperatures and whether SR59230A acts on BAT itself or via sympathetic neural control of BAT. Interscapular BAT (iBAT), brain, and body temperatures, tail artery blood flow, and heart rate were measured in unrestrained rats. SR59230A (1, 5, or 10 mg/kg ip), but not vehicle, decreased iBAT, body, and brain temperatures in a dose-dependent fashion (log-linear regression P < 0.01, R(2) = 0.3, 0.4, and 0.4, respectively, n = 10). Ultradian increases in BAT, brain, and body temperature were interrupted by administration of SR59230A (10 mg/kg ip) compared with vehicle, resuming after 162 ± 24 min (means ± SE, n = 10). SR59230A (10 mg/kg ip) caused a transient bradycardia without any increase in tail artery blood flow. In anesthetized rats, SR59230A reduced cooling-induced increases in iBAT temperature without affecting cooling-induced increases in iBAT sympathetic nerve discharge. Inhibition of BAT thermogenesis by SR59230A, thus, reflects direct blockade of beta-3 adrenoceptors in BAT. Interruption of episodic ultradian increases in body and brain temperature by SR59230A suggests that BAT thermogenesis makes a substantial contribution to these increases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activity Cycles / physiology*
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / physiology*
  • Adrenergic beta-3 Receptor Antagonists / pharmacology*
  • Animals
  • Body Temperature / drug effects
  • Body Temperature / physiology
  • Body Temperature Regulation / drug effects*
  • Body Temperature Regulation / physiology
  • Brain / drug effects
  • Brain / physiology*
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Male
  • Models, Animal
  • Propanolamines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology
  • Tail / blood supply
  • Thermogenesis / drug effects*
  • Thermogenesis / physiology

Substances

  • 3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate
  • Adrenergic beta-3 Receptor Antagonists
  • Propanolamines