title: In vivo beta3-adrenergic stimulation of human thermogenesis and lipid use.
abstract: OBJECTIVE
  To investigate the role of the human beta3-adrenergic receptor in in vivo isoproterenol (INN, isoprenaline)-induced thermogenesis and lipid use.
  
  
  METHODS
  Eight male volunteers participated in two studies. In the first study subjects received oral dosages of 2.5, 7.5, 15, and 40 mg nadolol or propranolol (both beta1- and beta2-adrenergic receptor antagonists) at random, after which isoproterenol (beta1-, beta2-, and beta3-adrenergic receptor agonist) was infused in an individually determined dosage (range, 19 to 35 ng/kg x min) that increased energy expenditure by 25% without pretreatment. In the second study, 50, 100, and 200 ng/kg x min isoproterenol or saline solution were infused after pretreatment with 80 mg nadolol. In both studies energy expenditure and respiratory exchange ratio were measured by indirect calorimetry and, at the end of each infusion period, blood samples were taken and tremor score (only first study), heart rate, and blood pressure were measured.
  
  
  RESULTS
  In the first study, nadolol or propranolol in doses < or =40 mg could not fully block beta1-adrenergic receptor-mediated increases in heart rate and systolic blood pressure. Propranolol in doses < or =7.5 mg could not fully block the beta2-adrenergic receptor-mediated increase in tremor score during isoproterenol infusion. The increases found in thermogenesis and lipid use could therefore be explained by concomitant beta1- and beta2-adrenergic stimulation. In the second study, isoproterenol infusion induced a significant increase in heart rate, but no increases in thermogenesis and lipid use were found compared with infusion of saline solution.
  
  
  CONCLUSIONS
  No evidence could be found for a beta3-adrenergic receptor-mediated increase in human thermogenesis and lipid use during isoproterenol infusion after pretreatment with nadolol or propranolol.
authors.affiliation: Nutrition Toxicology and Environment Research Institute Maastricht, Department of Human Biology, Maastricht University, The Netherlands. S.Schiffelers@hb.unimaas.nl
authors.forename: S L
authors.initials: SL
authors.lastname: Schiffelers
authors.forename: E E
authors.initials: EE
authors.lastname: Blaak
authors.forename: W H
authors.initials: WH
authors.lastname: Saris
authors.forename: M A
authors.initials: MA
authors.lastname: van Baak
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000704:Analysis of Variance; D001833:Body Temperature Regulation / Q000187:drug effects*; D002153:Calorimetry, Indirect; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008055:Lipids / Q000097:blood*; D008297:Male; D009248:Nadolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D012016:Reference Values; D012119:Respiration / Q000187:drug effects; D016037:Single-Blind Method
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D008055:Lipids; D011943:Receptors, Adrenergic, beta; D009248:Nadolol; D011433:Propranolol; D007545:Isoproterenol