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

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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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Abbreviations

BW:

Body weight

β2-agonist:

Beta2-adrenoceptor agonist

CI:

Confidence interval

DXA:

Dual-energy X-ray absorptiometry

EE:

Energy expenditure

\({\dot{\text{V}}\text{O}}_{{2{ \hbox{max} }}}\) :

Maximal oxygen uptake

RER:

Respiratory exchange ratio

MDL:

Method detection limit

RSD:

Relative standard deviation

SD:

Standardized mean difference

UPLC–MS/MS:

Ultra-performance liquid chromatography–mass spectrometer

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Acknowledgements

The authors would like to thank Jens Lund for many fruitful scientific discussions during the writing process and Dr. David Nichols (Central Science Laboratory, University of Tasmania) for conducting the UPLC–MS/MS instrumental analyses.

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Authors and Affiliations

  1. Section of Integrated Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, August Krogh, Universitetsparken 13, 2100, Copenhagen, Denmark

    Johan Onslev, Anders Kalsen, Søren Jessen, Jens Bangsbo & Morten Hostrup

  2. Department of Respiratory Research, Bispebjerg University Hospital, Copenhagen, Denmark

    Vibeke Backer, Anders Kalsen, Michael Kreiberg, Søren Jessen & Morten Hostrup

  3. IOC Research Center Copenhagen, Copenhagen, Denmark

    Vibeke Backer & Morten Hostrup

  4. Division of Pharmacy, School of Medicine, University of Tasmania, Hobart, Australia

    Glenn Jacobson & Christian Narkowicz

Authors
  1. Johan Onslev
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  2. Glenn Jacobson
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  3. Christian Narkowicz
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  4. Vibeke Backer
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  5. Anders Kalsen
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  8. Jens Bangsbo
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  9. Morten Hostrup
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Contributions

JO collected, analyzed, and interpreted the data, and drafted the manuscript. GJ developed and supervised the enantioselective UPLC–MS/MS analytical component of the study, including assay performance, analysis and reporting of results, as well as contributing to the final manuscript. CN undertook the UPLC–MS/MS sample preparation and method UPLC–MS/MS optimization, and reviewed the manuscript. VB was the responsible medical doctor of the study and performed medical examination of the subjects, and contributed to interpretation and review of the manuscript. AK, MK, and SJ conducted the human experiments and contributed to interpretation of the data and in drafting of the manuscript. JB and MH designed the study and contributed to data collection, analysis, interpretation, and in drafting of the manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Morten Hostrup.

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Funding

The study was supported by the Danish Ministry of Culture. The funder had no role in the design of the study, the collection, analysis, and interpretation of the data or the writing of the manuscript.

Conflict of interest

The authors declare that they have no conflicts of interest with the contents of this article.

Additional information

Communicated by Jean-René Lacour.

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Onslev, J., Jacobson, G., Narkowicz, C. et al. Beta2-adrenergic stimulation increases energy expenditure at rest, but not during submaximal exercise in active overweight men. Eur J Appl Physiol 117, 1907–1915 (2017). https://doi.org/10.1007/s00421-017-3679-9

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  • DOI: https://doi.org/10.1007/s00421-017-3679-9

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