An IL-6 promoter variant (-174 G/C) augments IL-6 production and alters skeletal muscle transcription in response to exercise in mice.

IF 3.3 3区 医学 Q1 PHYSIOLOGY
Journal of applied physiology Pub Date : 2025-01-01 Epub Date: 2024-12-12 DOI:10.1152/japplphysiol.00391.2024
L E Watson, C L MacRae, P Kallingappa, Y Cao, X Li, C P Hedges, R F D'Souza, N Fleming, K M Mellor, T L Merry
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引用次数: 0

Abstract

Interleukin-6 (IL-6) is produced and secreted by skeletal muscle cells during exercise and plays an important role in mediating metabolic responses to exercise. The promoter region of the IL-6 gene contains a common genetic variant (-174 G/C, rs1800795), which may alter responses to exercise training. To isolate the impact of this gene variant on exercise-induced IL-6 expression and skeletal muscle transcription responses following exercise, we generated knock-in mice with a GG or variant CC genotype for the murine homolog of rs1800795. The overall gross metabolic phenotype of resting mice was similar between genotypes; however, following acute treadmill running, the variant CC genotype was associated with a greater increase in skeletal muscle Il6 mRNA and circulating IL-6. Furthermore, we observed that mice with the variant CC genotype exhibited sex-specific differences in skeletal muscle master metabolism regulatory genes and had greater increases in genes controlling mitochondrial biogenesis in skeletal muscle post exercise. However, there was no effect of genotype on exercise-induced skeletal muscle glycogen depletion, circulating free fatty acids, blood glucose and lactate production, or exercise-responsive gene expression in subcutaneous fat. These findings suggest that the IL-6 promoter variant -174 G/C may result in enhanced skeletal muscle adaptations in response to exercise training and could mean that individuals with the "C" allele may more readily gain improvements in metabolic health in response to exercise training.NEW & NOTEWORTHY Interleukin-6 (IL-6) is produced and secreted by skeletal muscle during exercise and mediates metabolic responses to exercise. A common variant in the IL-6 promoter region (-174G/C) may alter responses to exercise training. Mice with the variant "CC" genotype exhibited higher skeletal muscle IL-6 mRNA and circulating IL-6 levels post exercise, as well as altered skeletal muscle gene transcription. This suggests that this variant might enhance muscle adaptations to exercise, potentially benefiting metabolic health.

IL-6启动子变体(-174 G/C)增加IL-6的产生并改变小鼠运动后骨骼肌的转录。
白介素-6 (Interleukin-6, IL-6)是骨骼肌细胞在运动过程中产生和分泌的物质,在调节运动代谢反应中起重要作用。IL-6基因的启动子区域包含一个常见的遗传变异(-174 G/C, rs1800795),这可能会改变对运动训练的反应。为了分离该基因变体对运动诱导的IL-6表达和运动后骨骼肌转录反应的影响,我们为rs1800795的小鼠同源物制造了GG或变异CC基因型的敲入小鼠。静息小鼠的总体总代谢表型在基因型之间相似;然而,急性跑步后,CC基因型变异与骨骼肌IL-6 mRNA和循环IL-6的显著增加相关。此外,我们观察到CC基因型变异的小鼠在骨骼肌主代谢调节基因中表现出性别特异性差异,并且在运动后骨骼肌中控制线粒体生物发生的基因增加更大。然而,基因型对运动诱导的骨骼肌糖原消耗、循环游离脂肪酸、血糖和乳酸生成或皮下脂肪中运动反应性基因表达没有影响。这些发现表明,IL-6启动子变异-174 G/C可能导致骨骼肌对运动训练的适应性增强,并且可能意味着具有“C”等位基因的个体可能更容易在运动训练中获得代谢健康的改善。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.00
自引率
9.10%
发文量
296
审稿时长
2-4 weeks
期刊介绍: The Journal of Applied Physiology publishes the highest quality original research and reviews that examine novel adaptive and integrative physiological mechanisms in humans and animals that advance the field. The journal encourages the submission of manuscripts that examine the acute and adaptive responses of various organs, tissues, cells and/or molecular pathways to environmental, physiological and/or pathophysiological stressors. As an applied physiology journal, topics of interest are not limited to a particular organ system. The journal, therefore, considers a wide array of integrative and translational research topics examining the mechanisms involved in disease processes and mitigation strategies, as well as the promotion of health and well-being throughout the lifespan. Priority is given to manuscripts that provide mechanistic insight deemed to exert an impact on the field.
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