Royal Melbourne Institute of Technology, Bundoora, Victoria, Australia.
Am J Physiol Regul Integr Comp Physiol. 2011 Jan;300(1):R175-82. doi: 10.1152/ajpregu.00338.2010. Epub 2010 Nov 3.
We have used a novel model of genetically imparted endurance exercise capacity and metabolic health to study the genetic and environmental contributions to skeletal muscle glucose and lipid metabolism. We hypothesized that metabolic abnormalities associated with low intrinsic running capacity would be ameliorated by exercise training. Selective breeding for 22 generations resulted in rat models with a fivefold difference in intrinsic aerobic capacity. Low (LCR)- and high (HCR)-capacity runners remained sedentary (SED) or underwent 6 wk of exercise training (EXT). Insulin-stimulated glucose transport, insulin signal transduction, and rates of palmitate oxidation were lower in LCR SED vs. HCR SED (P < 0.05). Decreases in glucose and lipid metabolism were associated with decreased β₂-adrenergic receptor (β₂-AR), and reduced expression of Nur77 target proteins that are critical regulators of muscle glucose and lipid metabolism [uncoupling protein-3 (UCP3), fatty acid transporter (FAT)/CD36; P < 0.01 and P < 0.05, respectively]. EXT reversed the impairments to glucose and lipid metabolism observed in the skeletal muscle of LCR, while increasing the expression of β₂-AR, Nur77, GLUT4, UCP3, and FAT/CD36 (P < 0.05) in this tissue. However, no metabolic improvements were observed following exercise training in HCR. Our results demonstrate that metabolic impairments resulting from genetic factors (low intrinsic aerobic capacity) can be overcome by an environmental intervention (exercise training). Furthermore, we identify Nur77 as a potential mechanism for improved skeletal muscle metabolism in response to EXT.
我们使用一种新型的遗传性耐力运动能力和代谢健康模型来研究骨骼肌葡萄糖和脂质代谢的遗传和环境贡献。我们假设与低固有跑步能力相关的代谢异常将通过运动训练得到改善。经过 22 代的选择性繁殖，产生了固有有氧能力相差五倍的大鼠模型。低（LCR）和高（HCR）能力的跑步者保持久坐（SED）或接受 6 周的运动训练（EXT）。与 HCR SED 相比，LCR SED 的胰岛素刺激葡萄糖转运、胰岛素信号转导和棕榈酸氧化率降低（P < 0.05）。葡萄糖和脂质代谢的降低与β₂-肾上腺素能受体（β₂-AR）减少以及肌肉葡萄糖和脂质代谢的关键调节蛋白 Nur77 靶蛋白的表达减少有关[解偶联蛋白-3（UCP3）、脂肪酸转运蛋白（FAT）/CD36；P < 0.01 和 P < 0.05]。EXT 逆转了 LCR 骨骼肌中观察到的葡萄糖和脂质代谢损伤，同时增加了该组织中β₂-AR、Nur77、GLUT4、UCP3 和 FAT/CD36 的表达（P < 0.05）。然而，在 HCR 中，运动训练后没有观察到代谢改善。我们的结果表明，遗传因素（低固有有氧能力）导致的代谢损伤可以通过环境干预（运动训练）克服。此外，我们确定 Nur77 是 EXT 响应改善骨骼肌代谢的潜在机制。
