A selective human beta3 adrenergic receptor agonist increases metabolic rate in rhesus monkeys

J Clin Invest. 1998 Jun 1;101(11):2387-93. doi: 10.1172/JCI2496.


Activation of beta3 adrenergic receptors on the surface of adipocytes leads to increases in intracellular cAMP and stimulation of lipolysis. In brown adipose tissue, this serves to up-regulate and activate the mitochondrial uncoupling protein 1, which mediates a proton conductance pathway that uncouples oxidative phosphorylation, leading to a net increase in energy expenditure. While chronic treatment with beta3 agonists in nonprimate species leads to uncoupling protein 1 up-regulation and weight loss, the relevance of this mechanism to energy metabolism in primates, which have much lower levels of brown adipose tissue, has been questioned. With the discovery of L-755,507, a potent and selective partial agonist for both human and rhesus beta3 receptors, we now demonstrate that acute exposure of rhesus monkeys to a beta3 agonist elicits lipolysis and metabolic rate elevation, and that chronic exposure increases uncoupling protein 1 expression in rhesus brown adipose tissue. These data suggest a role for beta3 agonists in the treatment of human obesity.

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • CHO Cells
  • Cricetinae
  • Female
  • Heart Rate / drug effects
  • Humans
  • Lipolysis / drug effects
  • Macaca mulatta
  • Male
  • Propanolamines / pharmacology
  • Receptors, Adrenergic, beta / drug effects*
  • Receptors, Adrenergic, beta-3
  • Sulfonamides / pharmacology*


  • Adrenergic beta-Agonists
  • L 755507
  • Propanolamines
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-3
  • Sulfonamides
  • CGP 12177