Paul Sebastian, Donath Lars, Hoppstädter Jessica, Hecksteden Anne
Department of Training Intervention Research, German Sport University Cologne, 50933, Cologne, Germany.
Institute of Physiology, Medical University of Innsbruck, 6020, Innsbruck, Austria.
Eur J Appl Physiol. 2025 Apr;125(4):1023-1036. doi: 10.1007/s00421-024-05644-7. Epub 2024 Nov 5.
Within human skeletal muscle, statin treatment leads to elevated levels of the glucocorticoid-induced leucine zipper (GILZ). Further, GILZ mediates the muscle-related side effects of statins. Physical exercise leads to GILZ suppression, in a mechanosensitive manner. Given that statin treatment is rarely tolerated by habitually exercising individuals due to statin-associated muscle symptoms (SAMS), it appears that the opposing regulation of GILZ facilitates this detrimental interaction of two key measures of cardiovascular prevention, specifically for exercise modalities with high muscle strain. Similarly, opposing regulation of atrophy associated genes (atrogenes) may be a further mechanism. If confirmed, these results might have implications for the exercise prescription of statin-users.
A systematic search of the Gene Expression Omnibus (GEO) repository for studies reporting the acute effects of either endurance (END), conventional resistance (RT), or eccentric resistance training (ECC) was conducted. GILZ, as well as the expression of pivotal atrogenes (e.g., muscle atrophy F-box, cathepsin L, etc.) were quantified.
15 studies with 204 participants (22 females; 182 males) were included. RT resulted in the highest GILZ suppression, significantly differing from the expressional change after END ( - 0.46 ± 1.11 vs. - 0.07 ± 1.08), but not from ECC ( - 0.46 ± 1.11 vs. - 0.46 ± 0.95). Similar results were seen for various atrogenes.
Our results strengthen the assumption that mechanical loading can be considered a key mediator of exercise-induced changes in GILZ and atrogene expression.
在人体骨骼肌中，他汀类药物治疗会导致糖皮质激素诱导亮氨酸拉链蛋白（GILZ）水平升高。此外，GILZ介导了他汀类药物的肌肉相关副作用。体育锻炼以机械敏感的方式导致GILZ受到抑制。鉴于习惯性锻炼的个体因他汀类药物相关肌肉症状（SAMS）而很少能耐受他汀类药物治疗，似乎GILZ的相反调节促成了心血管预防的两项关键措施之间的这种有害相互作用，特别是对于肌肉张力高的运动方式。同样，萎缩相关基因（atrogenes）的相反调节可能是另一种机制。如果得到证实，这些结果可能对他汀类药物使用者的运动处方有影响。
对基因表达综合数据库（GEO）进行系统检索，以查找报告耐力训练（END）、传统阻力训练（RT）或离心阻力训练（ECC）急性效应的研究。对GILZ以及关键atrogenes（如肌肉萎缩F盒蛋白、组织蛋白酶L等）的表达进行了定量分析。
纳入了15项研究，共204名参与者（22名女性；182名男性）。RT导致GILZ抑制程度最高，与END后的表达变化有显著差异（-0.46±1.11 vs. -0.07±1.08），但与ECC无显著差异（-0.46±1.11 vs. -0.46±0.95）。各种atrogenes也有类似结果。
我们的结果强化了这样一种假设，即机械负荷可被视为运动诱导的GILZ和atrogene表达变化的关键介质。
