The impact of mild hypoxia exposure on myokine secretion in human obesity

R.L.J. van Meijel; L.M.M. Vliex; S. Hartwig; S. Lehr; H. Al-Hasani; E.E. Blaak; G.H. Goossens

doi:10.1038/s41366-023-01294-5

The impact of mild hypoxia exposure on myokine secretion in human obesity

R.L.J. van Meijel, L.M.M. Vliex, S. Hartwig, S. Lehr, H. Al-Hasani, E.E. Blaak, G.H. Goossens^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background/ObjectiveCompelling evidence indicates that myokines act in an autocrine, paracrine and endocrine manner to alter metabolic homeostasis. The mechanisms underlying exercise-induced changes in myokine secretion remain to be elucidated. Since exercise acutely decreases oxygen partial pressure (pO(2)) in skeletal muscle (SM), the present study was designed to test the hypothesis that (1) hypoxia exposure impacts myokine secretion in primary human myotubes and (2) exposure to mild hypoxia in vivo alters fasting and postprandial plasma myokine concentrations in humans.MethodsDifferentiated primary human myotubes were exposed to different physiological pO(2) levels for 24 h, and cell culture medium was harvested to determine myokine secretion. Furthermore, we performed a randomized single-blind crossover trial to investigate the impact of mild intermittent hypoxia exposure (MIH: 7-day exposure to 15% O-2, 3x2h/day vs. normoxia: 21% O-2) on in vivo SM pO(2) and plasma myokine concentrations in 12 individuals with overweight and obesity (body-mass index >= 28 kg/m(2)).ResultsHypoxia exposure (1% O-2) increased secreted protein acidic and rich in cysteine (SPARC, p = 0.043) and follistatin like 1 (FSTL1, p = 0.021), and reduced leukemia inhibitory factor (LIF) secretion (p = 0.009) compared to 3% O-2 in primary human myotubes. In addition, 1% O-2 exposure increased interleukin-6 (IL-6, p = 0.004) and SPARC secretion (p = 0.021), whilst reducing fatty acid binding protein 3 (FABP3) secretion (p = 0.021) compared to 21% O-2. MIH exposure in vivo markedly decreased SM pO(2) (approximate to 40%, p = 0.002) but did not alter plasma myokine concentrations.ConclusionsHypoxia exposure altered the secretion of several myokines in primary human myotubes, revealing hypoxia as a novel modulator of myokine secretion. However, both acute and 7-day MIH exposure did not induce alterations in plasma myokine concentrations in individuals with overweight and obesity.

Original language	English
Pages (from-to)	520-527
Number of pages	8
Journal	International Journal of Obesity
Volume	47
Issue number	6
Early online date	1 Mar 2023
DOIs	https://doi.org/10.1038/s41366-023-01294-5
Publication status	Published - Jun 2023

Keywords

SKELETAL-MUSCLE
ADIPOSE-TISSUE
MYOGLOBIN DESATURATION
INSULIN-RESISTANCE
EXERCISE
INTERLEUKIN-6
EXPRESSION
SPARC
CELLS
AMPK

Access to Document

10.1038/s41366-023-01294-5

Cite this

@article{d0b3e1c34e384559936df0bb1faef63c,

title = "The impact of mild hypoxia exposure on myokine secretion in human obesity",

abstract = "Background/ObjectiveCompelling evidence indicates that myokines act in an autocrine, paracrine and endocrine manner to alter metabolic homeostasis. The mechanisms underlying exercise-induced changes in myokine secretion remain to be elucidated. Since exercise acutely decreases oxygen partial pressure (pO(2)) in skeletal muscle (SM), the present study was designed to test the hypothesis that (1) hypoxia exposure impacts myokine secretion in primary human myotubes and (2) exposure to mild hypoxia in vivo alters fasting and postprandial plasma myokine concentrations in humans.MethodsDifferentiated primary human myotubes were exposed to different physiological pO(2) levels for 24 h, and cell culture medium was harvested to determine myokine secretion. Furthermore, we performed a randomized single-blind crossover trial to investigate the impact of mild intermittent hypoxia exposure (MIH: 7-day exposure to 15% O-2, 3x2h/day vs. normoxia: 21% O-2) on in vivo SM pO(2) and plasma myokine concentrations in 12 individuals with overweight and obesity (body-mass index >= 28 kg/m(2)).ResultsHypoxia exposure (1% O-2) increased secreted protein acidic and rich in cysteine (SPARC, p = 0.043) and follistatin like 1 (FSTL1, p = 0.021), and reduced leukemia inhibitory factor (LIF) secretion (p = 0.009) compared to 3% O-2 in primary human myotubes. In addition, 1% O-2 exposure increased interleukin-6 (IL-6, p = 0.004) and SPARC secretion (p = 0.021), whilst reducing fatty acid binding protein 3 (FABP3) secretion (p = 0.021) compared to 21% O-2. MIH exposure in vivo markedly decreased SM pO(2) (approximate to 40%, p = 0.002) but did not alter plasma myokine concentrations.ConclusionsHypoxia exposure altered the secretion of several myokines in primary human myotubes, revealing hypoxia as a novel modulator of myokine secretion. However, both acute and 7-day MIH exposure did not induce alterations in plasma myokine concentrations in individuals with overweight and obesity.",

keywords = "SKELETAL-MUSCLE, ADIPOSE-TISSUE, MYOGLOBIN DESATURATION, INSULIN-RESISTANCE, EXERCISE, INTERLEUKIN-6, EXPRESSION, SPARC, CELLS, AMPK",

author = "{van Meijel}, R.L.J. and L.M.M. Vliex and S. Hartwig and S. Lehr and H. Al-Hasani and E.E. Blaak and G.H. Goossens",

note = "Funding Information: The authors would like to thank N. Hoebers and Y. Essers (Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+) for excellent technical support with cell culture experiments. Funding Information: This study was funded supported by a Senior Fellowship grant from the Dutch Diabetes Research Foundation (awarded to GG, grant number: 2015.82.1818) to GG and a Rising Star Award Fellowship (2014) from the European Foundation for the Study of Diabetes to GG. The funder was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report. Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2023",

month = jun,

doi = "10.1038/s41366-023-01294-5",

language = "English",

volume = "47",

pages = "520--527",

journal = "International Journal of Obesity",

issn = "0307-0565",

publisher = "Nature Publishing Group",

number = "6",

}

TY - JOUR

T1 - The impact of mild hypoxia exposure on myokine secretion in human obesity

AU - van Meijel, R.L.J.

AU - Vliex, L.M.M.

AU - Hartwig, S.

AU - Lehr, S.

AU - Al-Hasani, H.

AU - Blaak, E.E.

AU - Goossens, G.H.

N1 - Funding Information: The authors would like to thank N. Hoebers and Y. Essers (Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+) for excellent technical support with cell culture experiments. Funding Information: This study was funded supported by a Senior Fellowship grant from the Dutch Diabetes Research Foundation (awarded to GG, grant number: 2015.82.1818) to GG and a Rising Star Award Fellowship (2014) from the European Foundation for the Study of Diabetes to GG. The funder was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report. Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2023/6

Y1 - 2023/6

N2 - Background/ObjectiveCompelling evidence indicates that myokines act in an autocrine, paracrine and endocrine manner to alter metabolic homeostasis. The mechanisms underlying exercise-induced changes in myokine secretion remain to be elucidated. Since exercise acutely decreases oxygen partial pressure (pO(2)) in skeletal muscle (SM), the present study was designed to test the hypothesis that (1) hypoxia exposure impacts myokine secretion in primary human myotubes and (2) exposure to mild hypoxia in vivo alters fasting and postprandial plasma myokine concentrations in humans.MethodsDifferentiated primary human myotubes were exposed to different physiological pO(2) levels for 24 h, and cell culture medium was harvested to determine myokine secretion. Furthermore, we performed a randomized single-blind crossover trial to investigate the impact of mild intermittent hypoxia exposure (MIH: 7-day exposure to 15% O-2, 3x2h/day vs. normoxia: 21% O-2) on in vivo SM pO(2) and plasma myokine concentrations in 12 individuals with overweight and obesity (body-mass index >= 28 kg/m(2)).ResultsHypoxia exposure (1% O-2) increased secreted protein acidic and rich in cysteine (SPARC, p = 0.043) and follistatin like 1 (FSTL1, p = 0.021), and reduced leukemia inhibitory factor (LIF) secretion (p = 0.009) compared to 3% O-2 in primary human myotubes. In addition, 1% O-2 exposure increased interleukin-6 (IL-6, p = 0.004) and SPARC secretion (p = 0.021), whilst reducing fatty acid binding protein 3 (FABP3) secretion (p = 0.021) compared to 21% O-2. MIH exposure in vivo markedly decreased SM pO(2) (approximate to 40%, p = 0.002) but did not alter plasma myokine concentrations.ConclusionsHypoxia exposure altered the secretion of several myokines in primary human myotubes, revealing hypoxia as a novel modulator of myokine secretion. However, both acute and 7-day MIH exposure did not induce alterations in plasma myokine concentrations in individuals with overweight and obesity.

AB - Background/ObjectiveCompelling evidence indicates that myokines act in an autocrine, paracrine and endocrine manner to alter metabolic homeostasis. The mechanisms underlying exercise-induced changes in myokine secretion remain to be elucidated. Since exercise acutely decreases oxygen partial pressure (pO(2)) in skeletal muscle (SM), the present study was designed to test the hypothesis that (1) hypoxia exposure impacts myokine secretion in primary human myotubes and (2) exposure to mild hypoxia in vivo alters fasting and postprandial plasma myokine concentrations in humans.MethodsDifferentiated primary human myotubes were exposed to different physiological pO(2) levels for 24 h, and cell culture medium was harvested to determine myokine secretion. Furthermore, we performed a randomized single-blind crossover trial to investigate the impact of mild intermittent hypoxia exposure (MIH: 7-day exposure to 15% O-2, 3x2h/day vs. normoxia: 21% O-2) on in vivo SM pO(2) and plasma myokine concentrations in 12 individuals with overweight and obesity (body-mass index >= 28 kg/m(2)).ResultsHypoxia exposure (1% O-2) increased secreted protein acidic and rich in cysteine (SPARC, p = 0.043) and follistatin like 1 (FSTL1, p = 0.021), and reduced leukemia inhibitory factor (LIF) secretion (p = 0.009) compared to 3% O-2 in primary human myotubes. In addition, 1% O-2 exposure increased interleukin-6 (IL-6, p = 0.004) and SPARC secretion (p = 0.021), whilst reducing fatty acid binding protein 3 (FABP3) secretion (p = 0.021) compared to 21% O-2. MIH exposure in vivo markedly decreased SM pO(2) (approximate to 40%, p = 0.002) but did not alter plasma myokine concentrations.ConclusionsHypoxia exposure altered the secretion of several myokines in primary human myotubes, revealing hypoxia as a novel modulator of myokine secretion. However, both acute and 7-day MIH exposure did not induce alterations in plasma myokine concentrations in individuals with overweight and obesity.

KW - SKELETAL-MUSCLE

KW - ADIPOSE-TISSUE

KW - MYOGLOBIN DESATURATION

KW - INSULIN-RESISTANCE

KW - EXERCISE

KW - INTERLEUKIN-6

KW - EXPRESSION

KW - SPARC

KW - CELLS

KW - AMPK

U2 - 10.1038/s41366-023-01294-5

DO - 10.1038/s41366-023-01294-5

M3 - Article

C2 - 36997723

SN - 0307-0565

VL - 47

SP - 520

EP - 527

JO - International Journal of Obesity

JF - International Journal of Obesity

IS - 6

ER -