Divergent effects of an alpha2-adrenergic antagonist on lipolysis and thermogenesis: interactions with a beta3-adrenergic agonist in rats

Int J Mol Med. 2001 Jul;8(1):103-9.

Abstract

This study was undertaken in order to test the hypothesis that selective beta3-AR stimulation and simultaneous blockade of alpha2-AR would result in an increase of lipolysis and thermogenesis in rats. Incubation of isolated white adipocytes with the alpha2-AR antagonist yohimbine produced a concentration-dependent increase in glycerol release (P<0.001) for all assayed concentrations (10-12-10-6 M) and potentiated the lipolytic effect of the beta3-AR agonist Trecadrine. However, in vivo administration of yohimbine produced a marked decrease in body temperature (1.3-1.5 degrees C, P<0.001) and blocked the thermogenic effect of Trecadrine when simultaneously administered. A similar response was observed for whole body oxygen consumption. Furthermore, yohimbine did not modify brown adipose tissue oxygen consumption, but blocked the beta3-AR-mediated increase triggered by Trecadrine. Brown adipose tissue UCP-2 and -3 mRNA expression was not changed by yohimbine. In conclusion, the present work indicates that in vitro alpha2-AR blockade by yohimbine potentiates the beta3-AR-mediated stimulation of lipolysis. On the other hand, in vivo alpha2-AR antagonism blocks the thermogenic effects mediated by beta3-AR stimulation, suggesting a possible interplay between the receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Antagonists / pharmacology*
  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Benzyl Alcohols / pharmacology
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Temperature / drug effects
  • Carrier Proteins / genetics
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Gene Expression Regulation / drug effects
  • Glycerol / blood
  • Insulin / blood
  • Ion Channels
  • Leptin / metabolism
  • Lipolysis / drug effects*
  • Male
  • Membrane Proteins / genetics
  • Mitochondrial Proteins
  • Oxygen Consumption / drug effects
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Rectum / physiology
  • Thermogenesis / drug effects*
  • Uncoupling Protein 1
  • Yohimbine / pharmacology

Substances

  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Antagonists
  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-Agonists
  • Benzyl Alcohols
  • Blood Glucose
  • Carrier Proteins
  • Insulin
  • Ion Channels
  • Leptin
  • Membrane Proteins
  • Mitochondrial Proteins
  • RNA, Messenger
  • Uncoupling Protein 1
  • Yohimbine
  • trecadrine
  • Glycerol