Skeletal muscle characteristics of inherited low and high aerobic exercise capacity

Epidemiological studies reveal a strong link between low aerobic capacity and metabolic and cardiovascular diseases. Two-way artificial selection of rats based on low and high intrinsic exercise capacity has produced two strains that also differ in risk for metabolic syndrome (Koch LG, Britton SL. Artificial selection for intrinsic aerobic endurance running capacity in rats. Physiol Genomics 5:45-52, 2001). Here we investigated skeletal muscle characteristics and genotype-phenotype relationships behind high and low inherited aerobic exercise capacity and the link between oxygen metabolism and metabolic disease risk factors in rats derived from generation 18. This population (n=24) of high capacity runners (HCR) and low capacity runners (LCR) differed by 615% in maximal treadmill running capacity. LCR were significantly significantly heavier and had increased blood glucose, serum insulin and triglyceride concentration. HCR had higher resting metabolic rate than LCR. Capillaries/mm2 and capillary-to-fiber ratio were significantly greater in HCR rats in soleus and gastrocnemius and capillary-to-fiber ratio in extensor digitorum longus (EDL) muscle. Subsarcolemmal mitochondrial area was 96% (p<0.01) and intermyofibrillar area was 32% (p<0.05) larger in HCR soleus. Microarray results showed that 126 genes were significantly up-regulated and 113 genes were down-regulated in HCR (p<0.05). Functional clustering and unbiased correlation analysis of muscle microarray data revealed that genes up-regulated in HCR were related to mitochondria, carboxylic acid and lipid metabolism, and oxidoreductase activity. In conclusion, our data show that aerobic capacity is strongly linked to the architecture of energy transfer and corroborate the importance of oxygen metabolism as the determinant of metabolic health and complex metabolic diseases such as metabolic syndrome and type 2 diabetes.流行病学研究表明，低有氧能力与代谢性疾病及心血管疾病之间存在显著关联。研究人员根据大鼠固有运动能力的高低进行双向人工选择，培育出了代谢综合征风险存在显著差异的两个品系（Koch LG、Britton SL. 大鼠固有有氧耐力跑步能力的人工选择. 《生理基因组学》（Physiol Genomics）, 5卷:45-52, 2001）。本研究针对第18代繁育的大鼠，探究了遗传所得高、低有氧运动能力背后的骨骼肌特征及基因型-表型关联，同时分析了氧代谢与代谢疾病风险因子之间的联系。该群体共24只大鼠，分为高有氧能力大鼠（High Capacity Runner, HCR）与低有氧能力大鼠（Low Capacity Runner, LCR），二者的最大跑步机跑步能力相差615%。低有氧能力大鼠体重显著更高，血糖、血清胰岛素及甘油三酯浓度也显著升高。高有氧能力大鼠的静息代谢率高于低有氧能力大鼠。在比目鱼肌与腓肠肌中，高有氧能力大鼠的毛细血管密度（根/mm²）及毛细血管-肌纤维比值均显著更高；在趾长伸肌（Extensor Digitorum Longus, EDL）中，其毛细血管-肌纤维比值也显著更高。高有氧能力大鼠比目鱼肌的肌膜下线粒体面积增加了96%（p<0.01），肌原纤维间线粒体面积增加了32%（p<0.05）。微阵列（Microarray）检测结果显示，高有氧能力大鼠体内有126个基因显著上调，113个基因显著下调（p<0.05）。对骨骼肌微阵列数据进行功能聚类与无偏相关分析后发现，高有氧能力大鼠体内上调的基因与线粒体功能、羧酸及脂质代谢、氧化还原酶活性密切相关。综上，本研究数据表明，有氧能力与能量传递的结构基础密切相关，同时证实了氧代谢作为代谢健康及代谢综合征、2型糖尿病等复杂代谢疾病的决定因素的重要性。