title: Effect of a 28-d treatment with L-796568, a novel beta(3)-adrenergic receptor agonist, on energy expenditure and body composition in obese men.
abstract: BACKGROUND
  Stimulation of energy expenditure (EE) with selective thermogenic beta-adrenergic agonists may be a promising approach for treating obesity.
  
  
  OBJECTIVE
  We analyzed the effects of the highly selective human beta(3)-adrenergic agonist L-796568 on 24-h EE, substrate oxidation, and body composition in obese, weight-stable men.
  
  
  METHODS
  In this 2-center, double-blind, randomized, parallel-group study, we measured 24-h EE before and after 28 d of treatment with L-796568 (375 mg/d) or placebo during weight maintenance (ie, without dietary intervention) in nondiabetic, nonsmoking men aged 25-49 y with body mass index (in kg/m(2)) of 28-35 (n = 10 subjects per treatment group).
  
  
  RESULTS
  The mean change in 24-h EE from before to after treatment did not differ significantly between groups (92 +/- 586 and 86 +/- 512 kJ/24 h for the L-796568 and placebo groups, respectively). The change in 24-h nonprotein respiratory quotient from before to after treatment did not differ significantly between groups (0.009 +/- 0.021 and 0.009 +/- 0.029, respectively). No changes in glucose tolerance were observed, but triacylglycerol concentrations decreased significantly with L-796568 treatment compared with placebo (-0.76 +/- 0.76 and 0.42 +/- 0.31 mmol/L, respectively; P < 0.002). Overall, treatment-related changes in body composition were not observed, but higher plasma L-796568 concentrations in the L-796568 group were associated with greater decreases in fat mass (r = -0.69, P < 0.03).
  
  
  CONCLUSIONS
  Treatment with L-796568 for 28 d had no major lipolytic or thermogenic effect but it lowered triacylglycerol concentrations. This lack of chronic effect on energy balance is likely explained by insufficient recruitment of beta(3)-responsive tissues in humans, down-regulation of the beta(3)-adrenergic receptor-mediated effects with chronic dosing, or both.
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition / Q000187:drug effects*; D002153:Calorimetry, Indirect; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects*; D005215:Fasting; D005227:Fatty Acids / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000503:physiopathology*; D010919:Placebos; D013449:Sulfonamides / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood; D000096926:Benzenesulfonamides
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D001786:Blood Glucose; D002784:Cholesterol; D005227:Fatty Acids; D007328:Insulin; D010919:Placebos; D013449:Sulfonamides; D013844:Thiazoles; D014280:Triglycerides; C415563:N-(4-(2-((2-hydroxy-2-(3-pyridinyl)ethyl)amino)ethyl)phenyl)-4-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)benzenesulfonamide; D000096926:Benzenesulfonamides