Miura Shinji, Kai Yuko, Kamei Yasutomi, Bruce Clinton R, Kubota Naoto, Febbraio Mark A, Kadowaki Takashi, Ezaki Osamu
Nutritional Science Program, National Institute of Health and Nutrition, 1-23-1, Toyama, Shinjuku-ku, Tokyo 162-8636, Japan.
Am J Physiol Endocrinol Metab. 2009 Jan;296(1):E47-55. doi: 10.1152/ajpendo.90690.2008. Epub 2008 Oct 21.
A single bout of exercise increases glucose uptake and fatty acid oxidation in skeletal muscle, with a corresponding activation of AMP-activated protein kinase (AMPK). While the exercise-induced increase in glucose uptake is partly due to activation of AMPK, it is unclear whether the increase of fatty acid oxidation is dependent on activation of AMPK. To examine this, transgenic mice were produced expressing a dominant-negative (DN) mutant of alpha(1)-AMPK (alpha(1)-AMPK-DN) in skeletal muscle and subjected to treadmill running. alpha(1)-AMPK-DN mice exhibited a 50% reduction in alpha(1)-AMPK activity and almost complete loss of alpha(2)-AMPK activity in skeletal muscle compared with wild-type littermates (WT). The fasting-induced decrease in respiratory quotient (RQ) ratio and reduced body weight were similar in both groups. In contrast with WT mice, alpha(1)-AMPK-DN mice could not perform high-intensity (30 m/min) treadmill exercise, although their response to low-intensity (10 m/min) treadmill exercise was not compromised. Changes in oxygen consumption and the RQ ratio during sedentary and low-intensity exercise were not different between alpha(1)-AMPK-DN and WT. Importantly, at low-intensity exercise, increased fatty acid oxidation in response to exercise in soleus (type I, slow twitch muscle) or extensor digitorum longus muscle (type II, fast twitch muscle) was not impaired in alpha(1)-AMPK-DN mice, indicating that alpha(1)-AMPK-DN mice utilize fatty acid in the same manner as WT mice during low-intensity exercise. These findings suggest that an increased alpha(2)-AMPK activity is not essential for increased skeletal muscle fatty acid oxidation during endurance exercise.
单次运动可增加骨骼肌中的葡萄糖摄取和脂肪酸氧化，并相应激活AMP激活的蛋白激酶（AMPK）。虽然运动诱导的葡萄糖摄取增加部分归因于AMPK的激活，但脂肪酸氧化增加是否依赖于AMPK的激活尚不清楚。为了研究这一点，制备了在骨骼肌中表达α(1)-AMPK显性负性（DN）突变体（α(1)-AMPK-DN）的转基因小鼠，并使其进行跑步机跑步。与野生型同窝小鼠（WT）相比，α(1)-AMPK-DN小鼠骨骼肌中的α(1)-AMPK活性降低了50%，α(2)-AMPK活性几乎完全丧失。两组小鼠禁食诱导的呼吸商（RQ）比值降低和体重减轻情况相似。与WT小鼠不同，α(1)-AMPK-DN小鼠无法进行高强度（30米/分钟）的跑步机运动，尽管它们对低强度（10米/分钟）跑步机运动的反应未受影响。α(1)-AMPK-DN小鼠和WT小鼠在静息和低强度运动期间的耗氧量和RQ比值变化没有差异。重要的是，在低强度运动时，α(1)-AMPK-DN小鼠比目鱼肌（I型，慢肌纤维）或趾长伸肌（II型，快肌纤维）中因运动而增加的脂肪酸氧化并未受损，这表明α(1)-AMPK-DN小鼠在低强度运动期间利用脂肪酸的方式与WT小鼠相同。这些发现表明，在耐力运动期间，增加α(2)-AMPK活性对于增加骨骼肌脂肪酸氧化并非必不可少。
