Beta 2 -adrenergic stimulation increases energy expenditure at rest, but not during submaximal exercise in active overweight men

Abstract

Purpose

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.

Methods

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 × 27 µg). 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.

Results

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).

Conclusion

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.

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