Data_Sheet_1_Physiological and Biochemical Effects of Intrinsically High and Low Exercise Capacities Through Multiomics Approaches.docx

Regular exercise prevents lipid abnormalities and conditions such as diabetes mellitus, hypertension, and obesity; it considerably benefits sedentary individuals. However, individuals exhibit highly variable responses to exercise, probably due to genetic variations. Animal models are typically used to investigate the relationship of intrinsic exercise capacity with physiological, pathological, psychological, behavioral, and metabolic disorders. In the present study, we investigated differential physiological adaptations caused by intrinsic exercise capacity and explored the regulatory molecules or mechanisms through multiomics approaches. Outbred ICR mice (n = 100) performed an exhaustive swimming test and were ranked based on the exhaustive swimming time to distinguish intrinsically high- and low-capacity groups. Exercise performance, exercise fatigue indexes, glucose tolerance, and body compositions were assessed during the experimental processes. Furthermore, the gut microbiota, transcriptome, and proteome of soleus muscle with intrinsically high exercise capacity (HEC) and low exercise capacity (LEC) were further analyzed to reveal the most influential factors associated with differential exercise capacities. HEC mice outperformed LEC mice in physical activities (exhaustive swimming and forelimb grip strength tests) and exhibited higher glucose tolerance than LEC mice. Exercise-induced peripheral fatigue and the level of injury biomarkers (lactate, ammonia, creatine kinase, and aspartate aminotransferase) were also significantly lower in HEC mice than in LEC mice. Furthermore, the gut of the HEC mice contained significantly more Butyricicoccus than that of the LEC mice. In addition, transcriptome data of the soleus muscle revealed that the expression of microRNAs that are strongly associated with exercise performance-related physiological and metabolic functions (i.e., miR-383, miR-107, miR-30b, miR-669m, miR-191, miR-218, and miR-224) was higher in HEC mice than in LEC mice. The functional proteome data of soleus muscle indicated that the levels of key proteins related to muscle function and carbohydrate metabolism were also significantly higher in HEC mice than in LEC mice. Our study demonstrated that the mice with various intrinsic exercise capacities have different gut microbiome as well as transcriptome and proteome of soleus muscle by using multiomics approaches. The specific bacteria and regulatory factors, including miRNA and functional proteins, may be highly correlated with the adaptation of physiological functions and exercise capacity.

规律运动可预防脂质异常及糖尿病、高血压、肥胖等病症，对久坐人群亦具有显著益处。然而，个体对运动的响应存在高度异质性，这可能与遗传变异相关。动物模型通常被用于探究固有运动能力（intrinsic exercise capacity）与生理、病理、心理、行为及代谢紊乱之间的关联。本研究旨在探究固有运动能力所介导的差异性生理适应，并通过多组学（multiomics）方法解析其调控分子与机制。本研究选取100只远交系ICR小鼠，通过力竭游泳实验并以力竭游泳时长为依据进行分组，筛选出固有运动能力高（high-capacity, HEC）与低（low-capacity, LEC）的两组小鼠。实验过程中，我们对小鼠的运动表现、运动疲劳指标、葡萄糖耐受能力及体成分进行了检测。此外，我们进一步分析了高、低固有运动能力组小鼠比目鱼肌（soleus muscle）的肠道菌群、转录组与蛋白质组，以揭示与运动能力差异相关的关键影响因素。研究结果显示，相较于低运动能力组小鼠，高运动能力组小鼠在运动实验（力竭游泳与前肢握力测试）中表现更优，且葡萄糖耐受能力更强。运动诱导的外周疲劳程度以及损伤生物标志物（乳酸、氨、肌酸激酶与天冬氨酸转氨酶）水平，在高运动能力组小鼠中亦显著低于低运动能力组。此外，高运动能力组小鼠肠道内的丁酸球菌属（Butyricicoccus）丰度显著高于低运动能力组。同时，比目鱼肌的转录组数据分析显示，与运动表现相关的生理及代谢功能密切相关的microRNA（miR-383、miR-107、miR-30b、miR-669m、miR-191、miR-218及miR-224）在高运动能力组小鼠中的表达水平显著高于低运动能力组。比目鱼肌的功能蛋白质组数据表明，与肌肉功能及碳水化合物代谢相关的关键蛋白水平，在高运动能力组小鼠中同样显著高于低运动能力组。本研究通过多组学方法证实，不同固有运动能力的小鼠，其肠道菌群以及比目鱼肌的转录组与蛋白质组均存在显著差异。特定菌群与包括microRNA及功能蛋白在内的调控因子，或与生理功能适应及运动能力密切相关。