Patterson Dalton C, Birnbaum Allison, Matthews Ian, Cortes Constanza J
Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, California, USA.
Physiol Rep. 2025 Aug;13(16):e70519. doi: 10.14814/phy2.70519.
Running promotes skeletal muscle remodeling through metabolic and inflammatory signaling pathways, though the extent to which these responses are sex-dependent remains unclear. We profiled cytokine responses in quadriceps lysates from sedentary, voluntary wheel-running (VWR), and muscle-specific TFEB-overexpressing (cTFEB;HSACre) male and female mice. Cytokine analysis revealed 40 differentially expressed factors associated with exercise and/or TFEB overexpression, many exhibiting sex-dimorphic patterns. In males, VWR increased interleukins (IL-1α, IL-1β, IL-2, IL-5, and IL-17) and chemokines (e.g., MCP-1, CCL5, and CXCL9), including components of TNF signaling (e.g., TNFα, sTNFR1/2, and Fas ligand). These elevations were partially recapitulated by TFEB overexpression in sedentary males. In contrast, female VWR muscle showed limited changes, with significant differences restricted to IL-3, IL-3Rb, IL-13, and CXCL16. These findings demonstrate sex-specific cytokine responses to endurance-like stimuli and suggest a broader or more prolonged inflammatory remodeling profile in male skeletal muscle. Moreover, muscle-specific TFEB overexpression reproduced similar endurance-induced cytokine changes, particularly in males, highlighting TFEB as a partial molecular mimic of exercise-associated inflammatory signaling in skeletal muscle. Together, our data underscore the importance of sex as a biological variable in exercise-induced cytokine remodeling and support the utility of TFEB overexpression as a platform for prioritizing exercise-associated phenotypes.
跑步通过代谢和炎症信号通路促进骨骼肌重塑，不过这些反应在何种程度上存在性别差异尚不清楚。我们分析了久坐不动、自愿轮转跑步（VWR）以及肌肉特异性过表达转录因子EB（cTFEB;HSACre）的雄性和雌性小鼠股四头肌裂解物中的细胞因子反应。细胞因子分析揭示了40种与运动和/或转录因子EB过表达相关的差异表达因子，其中许多呈现出性别二态性模式。在雄性小鼠中，VWR增加了白细胞介素（IL-1α、IL-1β、IL-2、IL-5和IL-17）和趋化因子（如MCP-1、CCL5和CXCL9），包括肿瘤坏死因子信号通路的成分（如TNFα、sTNFR1/2和Fas配体）。久坐的雄性小鼠过表达转录因子EB部分重现了这些升高情况。相比之下，雌性VWR肌肉显示出有限的变化，显著差异仅限于IL-3、IL-3Rb、IL-13和CXCL16。这些发现证明了对耐力样刺激的性别特异性细胞因子反应，并表明雄性骨骼肌中存在更广泛或更持久的炎症重塑特征。此外，肌肉特异性过表达转录因子EB重现了类似的耐力诱导的细胞因子变化，特别是在雄性小鼠中，这突出了转录因子EB作为骨骼肌中运动相关炎症信号的部分分子模拟物的作用。总之，我们的数据强调了性别作为运动诱导的细胞因子重塑中的生物学变量的重要性，并支持将过表达转录因子EB作为确定运动相关表型优先级的平台的实用性。
