Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands.
Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
Int J Obes (Lond). 2023 Jun;47(6):520-527. doi: 10.1038/s41366-023-01294-5. Epub 2023 Mar 30.
BACKGROUND/OBJECTIVE: Compelling 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) 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.
Differentiated primary human myotubes were exposed to different physiological pO 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, 3x2h/day vs. normoxia: 21% O) on in vivo SM pO and plasma myokine concentrations in 12 individuals with overweight and obesity (body-mass index ≥ 28 kg/m).
Hypoxia exposure (1% O) 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 in primary human myotubes. In addition, 1% O 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. MIH exposure in vivo markedly decreased SM pO (≈40%, p = 0.002) but did not alter plasma myokine concentrations.
Hypoxia 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.
This study is registered at the Netherlands Trial Register (NL7120/NTR7325).
背景/目的：大量证据表明肌因子以自分泌、旁分泌和内分泌的方式发挥作用，改变代谢稳态。运动引起的肌因子分泌变化的机制仍有待阐明。由于运动可使骨骼肌（SM）中的氧分压（pO ）急性降低，本研究旨在检验以下假设：（1）缺氧暴露会影响原代人肌管中的肌因子分泌；（2）体内轻度缺氧暴露会改变超重和肥胖人群的空腹和餐后血浆肌因子浓度。
将分化的原代人肌管分别暴露于不同的生理 pO 水平 24 小时，然后收获细胞培养液以确定肌因子的分泌情况。此外，我们进行了一项随机单盲交叉试验，以研究轻度间歇性缺氧暴露（MIH：7 天暴露于 15% O ，3x2h/天与常氧：21% O ）对 12 名超重和肥胖个体（体重指数≥28kg/m ）体内 SM pO 和血浆肌因子浓度的影响。
与 3% O 相比，缺氧暴露（1% O ）可增加原代人肌管中分泌蛋白酸性和富含半胱氨酸（SPARC，p=0.043）和卵泡抑素样 1（FSTL1，p=0.021）的分泌，并减少白血病抑制因子（LIF）的分泌（p=0.009）。此外，1% O 暴露可增加白细胞介素-6（IL-6，p=0.004）和 SPARC 的分泌（p=0.021），同时减少脂肪酸结合蛋白 3（FABP3）的分泌（p=0.021），而与 21% O 相比。体内 MIH 暴露显著降低 SM pO（≈40%，p=0.002），但不改变血浆肌因子浓度。
缺氧暴露改变了原代人肌管中几种肌因子的分泌，揭示了缺氧是肌因子分泌的一种新的调节剂。然而，急性和 7 天 MIH 暴露均未引起超重和肥胖个体血浆肌因子浓度的变化。
本研究在荷兰临床试验注册中心（NL7120/NTR7325）注册。
