Beta2-adrenergic stimulation increases energy expenditure at rest, but not during submaximal exercise in active overweight men.

Abstract

β2-Agonists have been proposed as weight-loss treatment, because they elevate energy expenditure. However, it is unknown what effect β2-agonists have on energy expenditure in overweight individuals. Furthermore, the influence of β2-agonist R- and S-enantiomer ratio for the increased energy expenditure is insufficiently explored. Nineteen males were included in the study of which 14 completed. Subjects were 31.6 (±3.5)years [mean (±95% CI)] and had a fat percentage of 22.7 (±2.1)%. On separate days, subjects received either placebo or inhaled racemic (rac-) formoterol (2×27µg). After an overnight fast, energy expenditure and substrate oxidation were estimated by indirect calorimetry at rest and during submaximal exercise. Plasma (R,R)- and (S,S)-formoterol enantiomer levels were measured by ultra-performance liquid chromatograph-mass spectrometry. At rest, energy expenditure and fat oxidation were 12% (P≤0.001) and 38% (P=0.006) higher for rac-formoterol than placebo. Systemic (R,R):(S,S) formoterol ratio was correlated with change in energy expenditure at rest in response to rac-formoterol (r=0.63, P=0.028), whereas no association was observed between fat percentage and rac-formoterol-induced change in energy expenditure. During exercise, energy expenditure was not different between treatments, although carbohydrate oxidation was 15% higher (P=0.021) for rac-formoterol than placebo. Rac-formoterol-induced shift in substrate choice from rest to exercise was related to plasma ln-rac-formoterol concentrations (r=0.75, P=0.005). Selective β2-adrenoceptor agonism effectively increases metabolic rate and fat oxidation in overweight individuals. The potential for weight loss induced by β2-agonists may be greater for R-enantiopure formulations.