Spargo Fiona J, McGee Sean L, Dzamko Nick, Watt Matthew J, Kemp Bruce E, Britton Steven L, Koch Lauren G, Hargreaves Mark, Hawley John A
Exercise Metabolism Group, School of Medical Sciences, Australia.
Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1631-6. doi: 10.1152/ajpendo.00702.2006. Epub 2007 Feb 6.
As substrate for evaluation of metabolic diseases, we developed novel rat models that contrast for endurance exercise capacity. Through two-way artificial selection, we created rodent phenotypes of intrinsically low-capacity runners (LCR) and high-capacity runners (HCR) that also differed markedly for cardiovascular and metabolic disease risk factors. Here, we determined skeletal muscle proteins with putative roles in lipid and carbohydrate metabolism to better understand the mechanisms underlying differences in whole body substrate handling between phenotypes. Animals (generation 16) differed for endurance running capacity by 295%. LCR animals had higher resting plasma glucose (6.58 +/- 0.45 vs. 6.09 +/- 0.45 mmol/l), insulin (0.48 +/- 0.03 vs. 0.32 +/- 0.02 ng/ml), nonesterified fatty acid (0.57 +/- 0.14 v 0.35 +/- 0.05 mM), and triglyceride (TG; 0.47 +/- 0.11 vs. 0.25 +/- 0.08 mmol/l) concentrations (all P < 0.05). Muscle TG (72.3 +/- 14.7 vs. 38.9 +/- 6.2 mmol/kg dry muscle wt; P < 0.05) and diacylglycerol (96 +/- 28 vs. 42 +/- 8 pmol/mg dry muscle wt; P < 0.05) contents were elevated in LCR vs. HCR rats. Accompanying the greater lipid accretion in LCR was increased fatty acid translocase/CD36 content (1,014 +/- 80 vs. 781 +/- 70 arbitrary units; P < 0.05) and reduced TG lipase activity (0.158 +/- 0.0125 vs. 0.274 +/- 0.018 mmol.min(-1).kg dry muscle wt(-1); P < 0.05). Muscle glycogen, GLUT4 protein, and basal phosphorylation states of AMP-activated protein kinase-alpha1, AMP-activated protein kinase-alpha2, and acetyl-CoA carboxylase were similar in LCR and HCR. In conclusion, rats with low intrinsic aerobic capacity demonstrate abnormalities in lipid-handling capacity. These disruptions may, in part, be responsible for the increased risk of metabolic disorders observed in this phenotype.
作为评估代谢性疾病的底物，我们开发了具有不同耐力运动能力的新型大鼠模型。通过双向人工选择，我们培育出了内在低运动能力跑步者（LCR）和高运动能力跑步者（HCR）的啮齿动物表型，它们在心血管和代谢疾病风险因素方面也存在显著差异。在此，我们确定了在脂质和碳水化合物代谢中可能起作用的骨骼肌蛋白质，以更好地理解不同表型之间全身底物处理差异的潜在机制。动物（第16代）的耐力跑步能力相差295%。LCR动物的静息血浆葡萄糖（6.58±0.45 vs. 6.09±0.45 mmol/l）、胰岛素（0.48±0.03 vs. 0.32±0.02 ng/ml）、非酯化脂肪酸（0.57±0.14 vs 0.35±0.05 mM）和甘油三酯（TG；0.47±0.11 vs. 0.25±0.08 mmol/l）浓度均更高（所有P<0.05）。与HCR大鼠相比，LCR大鼠肌肉中的TG（72.3±14.7 vs. 38.9±6.2 mmol/kg干肌肉重量；P<0.05）和二酰基甘油（96±28 vs. 42±8 pmol/mg干肌肉重量；P<0.05）含量升高。伴随着LCR中脂质积累的增加，脂肪酸转位酶/CD36含量增加（1014±80 vs. 781±70任意单位；P<0.05），TG脂肪酶活性降低（0.158±0.0125 vs. 0.274±0.018 mmol·min-1·kg干肌肉重量-1；P<0.05）。LCR和HCR大鼠的肌肉糖原、GLUT4蛋白以及AMP激活的蛋白激酶-α1、AMP激活的蛋白激酶-α2和乙酰辅酶A羧化酶的基础磷酸化状态相似。总之，内在有氧能力低的大鼠在脂质处理能力方面表现异常。这些紊乱可能部分导致了该表型中观察到的代谢紊乱风险增加。
