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

Am J Clin Nutr. 2002 Oct;76(4):780-8. doi: 10.1093/ajcn/76.4.780.

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.

Design: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-3 Receptor Agonists*
  • Adult
  • Blood Glucose / analysis
  • Body Composition / drug effects*
  • Calorimetry, Indirect
  • Cholesterol / blood
  • Diet
  • Double-Blind Method
  • Energy Metabolism / drug effects*
  • Fasting
  • Fatty Acids / blood
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood
  • Kinetics
  • Male
  • Middle Aged
  • Obesity / physiopathology*
  • Placebos
  • Sulfonamides / pharmacology*
  • Thiazoles / pharmacology*
  • Triglycerides / blood

Substances

  • Adrenergic beta-3 Receptor Agonists
  • Blood Glucose
  • Fatty Acids
  • Insulin
  • N-(4-(2-((2-hydroxy-2-(3-pyridinyl)ethyl)amino)ethyl)phenyl)-4-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)benzenesulfonamide
  • Placebos
  • Sulfonamides
  • Thiazoles
  • Triglycerides
  • Cholesterol