Atypical beta-adrenoceptor on brown adipocytes as target for anti-obesity drugs

Nature. 1984 May;309(5964):163-5. doi: 10.1038/309163a0.

Abstract

Recent studies suggest that thermogenesis in brown adipose tissue has an important role in the regulation of energy balance. Thermogenesis is effected by noradrenaline released from sympathetic nerve endings; the noradrenaline stimulates beta-adrenoceptors, causing lipolysis, and the released fatty acids then promote the uncoupling of oxidative phosphorylation from electron transport. It has been widely accepted that mammalian beta-adrenoceptors exist as two subtypes, beta 1 and beta 2, and rat brown adipocyte beta-adrenoceptors have been classed as beta 1 or as a mixed beta 1/beta 2 population. The beta 1 subtype predominates in atria, whereas the beta 2 subtype predominates in trachea. However, we have now found a novel group of beta-adrenoceptor agonists that selectively stimulate lipolysis in brown adipocytes. In contrast, isoprenaline, fenoterol and salbutamol are less potent as stimulants of lipolysis than as stimulants of atrial rate or tracheal relaxation. Therefore, beta-adrenoceptors in rat brown adipocytes are of neither the beta 1 nor beta 2 subtypes. Compounds that selectively stimulate brown adipocyte beta-adrenoceptors should have potential as thermogenic anti-obesity agents and this has been demonstrated with BRL 26830A , BRL 33725A and BRL 35135A .

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / physiology*
  • Albuterol / pharmacology
  • Animals
  • Appetite Depressants / pharmacology*
  • Body Temperature Regulation / drug effects
  • Female
  • Fenoterol / pharmacology
  • Heart Rate / drug effects
  • Isoproterenol / pharmacology
  • Kinetics
  • Lipolysis / drug effects
  • Mice
  • Mice, Obese
  • Muscle Relaxation / drug effects
  • Rats
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / physiology*
  • Structure-Activity Relationship
  • Trachea / physiology

Substances

  • Appetite Depressants
  • Receptors, Adrenergic, beta
  • Fenoterol
  • Isoproterenol
  • Albuterol