Research Unit of Genetics and Biometry, Leibniz-Institute for Farm Animal Biology, Dummerstorf, Germany.
Med Sci Sports Exerc. 2013 May;45(5):841-50. doi: 10.1249/MSS.0b013e31827e0fca.
Long-distance runners have increased needs of energy supply. To unravel genetically based mechanisms required for efficient energy supply, we have analyzed hepatic metabolism of mice characterized by the inborn capacity to perform as long-distance runners.
The mouse model had been established by phenotypic selection for high treadmill performance for 90 generations and was characterized by approximately 3.8-fold higher running capacities (Dummerstorf high Treadmill Performance mouse line [DUhTP]) compared with unselected and also untrained controls (Dummerstorf Control mouse line [DUC]). From 7-wk-old male mice, serum and liver samples were collected and analyzed for messenger RNA, protein, and metabolite levels, respectively.
In livers from DUhTP mice, we identified significantly higher messenger RNA transcript levels of peroxisome proliferator-activated receptor delta and higher protein levels of sirtuin-1, acetyl-CoA-synthetase, acetyl-CoA-carboxylase, phosphoenolpyruvate carboxykinase, and glutamate-dehydrogenase, suggesting higher gluconeogenesis and lipogenesis in DUhTP mice. In fact, higher hepatic levels of glycogen and triglycerides as well as higher concentrations of carbohydrate, fatty acid, and cholesterol metabolites were found in DUhTP mice. In parallel, in DUhTP mice, which did not have access to running wheels, a marked hyperlipidemia (cholesterol = 160% ± 8%, triglycerides = 174% ± 14% of controls, respectively), and abdominal obesity (DUhTP = 0.396 ± 0.019 g, DUC = 0.291 ± 0.019 g) were found.
From our data, we conclude that the physiological basis of genetically fixed higher endurance-running performance in DUhTP marathon mouse is related to increased hepatic gluconeogenesis and lipogenesis. Expression of sirtuin 1 as well as of gluconeogenic and lipogenic key enzymes may be related to peroxisome proliferator-activated receptor delta. Metabolic adaptations presented in our study represent inborn features of superior endurance-running performance.
长跑运动员对能量供应的需求增加。为了揭示高效能量供应所需的基于遗传的机制，我们分析了具有内在长距离跑步能力的小鼠的肝脏代谢。
通过表型选择，对 90 代小鼠进行了高跑步机性能的特征选择，从而建立了该小鼠模型，与未经选择且未经训练的对照组（Dummerstorf 对照鼠系[DUC]）相比，其跑步能力提高了约 3.8 倍（Dummerstorf 高跑步机性能鼠系[DUhTP]）。从小鼠 7 周龄雄性小鼠中采集血清和肝组织样本，分别用于检测信使 RNA、蛋白质和代谢物水平。
在 DUhTP 小鼠的肝脏中，我们发现过氧化物酶体增殖物激活受体δ的信使 RNA 转录水平显著升高，SIRT1 蛋白水平升高，乙酰辅酶 A-合成酶、乙酰辅酶 A-羧化酶、磷酸烯醇丙酮酸羧激酶和谷氨酸脱氢酶的蛋白水平升高，表明 DUhTP 小鼠的糖异生和脂肪生成增加。事实上，在 DUhTP 小鼠的肝脏中发现了更高水平的糖原和甘油三酯，以及更高水平的碳水化合物、脂肪酸和胆固醇代谢物。与此平行，在 DUhTP 小鼠中，即使没有机会使用跑步轮，也会发现明显的高脂血症（胆固醇= 160%±8%，甘油三酯= 174%±14%，分别为对照组的）和腹部肥胖（DUhTP=0.396±0.019 g，DUC=0.291±0.019 g）。
从我们的数据中可以得出结论，DUhTP 马拉松小鼠中基因固定的更高耐力跑步性能的生理基础与肝脏糖异生和脂肪生成增加有关。SIRT1 的表达以及糖异生和脂肪生成的关键酶可能与过氧化物酶体增殖物激活受体δ有关。我们研究中呈现的代谢适应是卓越耐力跑步性能的固有特征。
