Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise
Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise
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DOI：
10.1152/ajpendo.00379.2004
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发表时间：
2005-01-01
影响因子：
5.1
通讯作者：
Kiens, B
中科院分区：
文献类型：
--
作者：
Roepstorff, C;Halberg, N;Kiens, B
研究了运动过程中人体骨骼肌脂肪氧化的细胞内调节机制。8名年轻、健康、受过适度训练的男性进行了两次自行车运动（60分钟，65%峰值O-2消耗），在运动前他们摄入1）高碳水化合物饮食（H-CHO）或2）低碳水化合物饮食（L-CHO），以改变肌肉糖原含量，并分别诱导低和高脂肪氧化率。在运动过程中，L-CHO组的腿部脂肪氧化比H-CHO组高122%（P < 0.001）。与此相一致的是，运动60 min时，L-CHO中α（2）-AMPK活性比H-CHO中增加了2倍（P < 0.01）。然而，乙酰辅酶A羧化酶（ACC）β Ser（221）磷酸化在两种条件下增加到相同的程度（6倍）。两种运动状态下丙二酰辅酶A浓度均降低13%（P < 0.05）。丙酮酸脱氢酶活性在运动过程中H-CHO组高于L-CHO组（P < 0.01）。运动后，仅在H-CHO中，乙酰辅酶A和乙酰肉毒碱浓度升高（P < 0.001），游离肉毒碱浓度降低（P < 0.01）。这些数据表明，丙二酰辅酶A浓度的降低，继发于α（2）-AMPK激活和ACC抑制（通过磷酸化），有助于在运动开始时观察到的脂肪氧化的增加，而与肌糖原水平无关。他们还认为，在高肌糖原的情况下，游离肉碱的可用性可能会限制运动过程中的脂肪氧化，因为它增加了乙酰肉碱的形成。
Intracellular mechanisms regulating fat oxidation were investigated in human skeletal muscle during exercise. Eight young, healthy, moderately trained men performed bicycle exercise (60 min, 65% peak O-2 consumption) on two occasions, where they ingested either 1) a high-carbohydrate diet (H-CHO) or 2) a low-carbohydrate diet (L-CHO) before exercise to alter muscle glycogen content as well as to induce, respectively, low and high rates of fat oxidation. Leg fat oxidation was 122% higher during exercise in L-CHO than in H-CHO ( P < 0.001). In keeping with this, the activity of α(2)-AMP-activated protein kinase (α(2)-AMPK) was increased twice as much in L-CHO as in H-CHO ( P < 0.01) at 60 min of exercise. However, acetyl-CoA carboxylase (ACC)beta Ser(221) phosphorylation was increased to the same extent (6-fold) under the two conditions. The concentration of malonyl-CoA was reduced 13% by exercise in both conditions ( P < 0.05). Pyruvate dehydrogenase activity was higher during exercise in H-CHO than in L-CHO ( P < 0.01). In H-CHO only, the concentrations of acetyl-CoA and acetylcarnitine were increased ( P < 0.001), and the concentration of free carnitine was decreased ( P < 0.01), by exercise. The data suggest that a decrease in the concentration of malonyl-CoA, secondary to alpha(2)-AMPK activation and ACC inhibition ( by phosphorylation), contributes to the increase in fat oxidation observed at the onset of exercise regardless of muscle glycogen levels. They also suggest that, with high muscle glycogen, the availability of free carnitine may limit fat oxidation during exercise, due to its increased use for acetylcarnitine formation.