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Clinical Research

Hypoxia and exercise interactions on skeletal muscle insulin sensitivity in obese subjects with metabolic syndrome: results of a randomized controlled trial

International Journal of Obesity volume 44, pages 1119–1128 (2020)Cite this article

Subjects

Abstract

Background

Physical activity improves insulin sensitivity in obesity. Hypoxia training is claimed to augment this effect. We tested the hypothesis that normobaric hypoxia training would improve insulin sensitivity in obese patients with metabolic syndrome.

Methods

In a randomized controlled trial, 23 obese men with metabolic syndrome who were not informed of the FiO2 conditions underwent a 6-week physical exercise intervention under ambient (n = 11; FiO2 21%) conditions or hypoxia (n = 12; FiO2 15%) using a normobaric hypoxic chamber. Three 60-min sessions of interval training were performed each week at 60% of individual V̇O2max. Assessment of myocellular insulin sensitivity by euglycemic hyperinsulinemic clamp was performed in 21 of these subjects before and after 6 weeks of training. Comprehensive phenotyping also included biopsies of subcutaneous adipose tissues.

Results

The intermittent moderate physical exercise protocol did not substantially change the myocellular insulin sensitivity within 6 weeks under normoxic conditions (ISIClamp: 0.035 (IQR 0.016–0.075) vs. 0.037 (IQR 0.026–0.056) mg* kg−1 *min−1/(mU* l−1); p = 0.767). In contrast, ISIClamp improved during hypoxia training (0.028 (IQR 0.018–0.035) vs. 0.038 (IQR 0.024–0.060) mg * kg−1 *min−1/(mU *l−1); p < 0.05). Between group comparison of ISIClamp change revealed a small difference between groups (Cohen's d = 0.26). Within the hypoxic group, improvement of ISIClamp during training was associated with individual increase of circulating vascular endothelial growth factor (VEGF) levels (r = 0.678, p = 0.015), even if mean VEGF levels were not modified by any training condition. Atrial natriuretic peptide (ANP) system components were not associated with increased ISIClamp during hypoxic training.

Conclusions

Physical training under hypoxic conditions could partially augment the favorable effects of exercise alone on myocellular insulin sensitivity in obese men with metabolic syndrome. Concomitant changes in VEGF might represent an underlying pathophysiological mechanism.

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Fig. 1
Fig. 2: ISIClamp before and after a moderate 6-week training under either normobaric normoxic (n = 9) or hypoxic (n = 12) conditions.
Fig. 3: Adipose NPR-A/NPR-C ratio before and after a moderate 6-week training under either normobaric normoxic (n = 9) or hypoxic conditions (n = 12).
Fig. 4

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Gabriele Rahn, N. Huckauf, and C. Kalischke for excellent technical assistance.

Funding

This research was supported by the Deutsche Forschungsgemeinschaft (LU 435/13-1). KM was supported by the German Diabetes Society (DDG) and the German Ministry for Education and Research (BMBF) by support of the Berlin Institute of Health (BIH).

Author information

Authors and Affiliations

  1. Experimental and Clinical Research Center (ECRC), a joint collaboration between the Max-Delbrück Center for Molecular Medicine and the Charité Universitätsmedizin, Berlin, Germany, and Helios Clinics Berlin, Berlin, Germany

    Knut Mai, Lars Klug, Natalia Rakova, Anja Mähler, Jeanette Schulz-Menger, Joachim Spranger, Michael Boschmann & Friedrich C. Luft

  2. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Clinic of Endocrinology, Diabetes & Nutrition, Berlin, Germany

    Knut Mai, Thomas Bobbert & Joachim Spranger

  3. Charité-Center for Cardiovascular Research (CCR), Berlin, Germany

    Knut Mai & Joachim Spranger

  4. DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany

    Knut Mai & Joachim Spranger

  5. Berlin Institute of Health (BIH), Anna-Louisa-Karsch Str. 2, 10178, Berlin, Germany

    Knut Mai & Sophie K. Piper

  6. Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Biometry and Clinical Epidemiology, Berlin, Germany

    Sophie K. Piper

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Contributions

NR, MB, LK, AM, TB, and JSM researched data. KM researched data and was primarily responsible for writing the manuscript. TB, MB, SP, AM, LK, JS, and FCL contributed to the discussion and reviewed/edited the manuscript. FCL conceived the study and obtained funding.

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Correspondence to Knut Mai.

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The study protocols were approved by the Institutional Review Board of the Charité Medical School (EA1/140/12) and all subjects gave written informed consent.

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Mai, K., Klug, L., Rakova, N. et al. Hypoxia and exercise interactions on skeletal muscle insulin sensitivity in obese subjects with metabolic syndrome: results of a randomized controlled trial. Int J Obes 44, 1119–1128 (2020). https://doi.org/10.1038/s41366-019-0504-z

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