Exercise training decreases the concentration of malonyl-CoA and increases the expression and activity of malonyl-CoA decarboxylase in human muscle
Exercise training decreases the concentration of malonyl-CoA and increases the expression and activity of malonyl-CoA decarboxylase in human muscle
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DOI：
10.1152/ajpendo.00341.2005
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发表时间：
2006-06-01
影响因子：
5.1
通讯作者：
Bavenholm, Peter N.
中科院分区：
文献类型：
--
作者：
Kuhl, Jeanette E.;Ruderman, Neil B.;Bavenholm, Peter N.
本研究旨在评估体力训练是否会导致人体肌肉中丙二酰辅酶A及其调控浓度的酶发生变化。对健康的中年受试者在一项为期12周的训练计划前后进行了研究，该训练计划使最大摄氧量（Vo(2) (max)）显著提高了13%，腹部内脂肪减少了17%。在训练后，即最后一次运动后的24 - 36小时，观察到丙二酰辅酶A浓度显著降低（25 - 30%）。同时，肌肉中丙二酰辅酶A脱羧酶（MCD）的活性增加了88%，其信使核糖核酸（mRNA）增加了51%，但腺苷酸活化蛋白激酶（AMPK，苏氨酸172位点）或乙酰辅酶A羧化酶的磷酸化没有变化。过氧化物酶体增殖物激活受体γ辅激活因子 - 1α（PGC - 1α）的含量也增加了（3倍），PGC - 1α是一种转录调节因子，与过氧化物酶体增殖物激活受体γ介导的MCD表达有关。在同样于最后一次运动后的24 - 36小时进行的研究中，在正常血糖 - 高胰岛素钳夹试验期间，未观察到全身胰岛素敏感性或脂肪酸氧化增加的证据。总之，体力训练后肌肉中丙二酰辅酶A的浓度降低，很可能是因为PGC - 1α介导的MCD表达和活性增加。在健康个体中，急性运动通常会导致AMPK活性以及全身胰岛素敏感性和脂肪酸氧化增加，而这些变化在这些增加消失后仍然存在。
The study was designed to evaluate whether changes in malonyl-CoA and the enzymes that govern its concentration occur in human muscle as a result of physical training. Healthy, middle-aged subjects were studied before and after a 12-wk training program that significantly increased Vo(2) (max) by 13% and decreased intra-abdominal fat by 17%. Significant decreases (25-30%) in the concentration of malonyl-CoA were observed after training, 24-36 h after the last bout of exercise. They were accompanied by increases in both the activity (88%) and mRNA (51%) of malonyl-CoA decarboxylase (MCD) in muscle but no changes in the phosphorylation of AMP kinase (AMPK, Thr172) or of acetyl-CoA carboxylase. The abundance of peroxisome proliferator-activated receptor (PPAR)gamma coactivator-1 alpha (PGC-1 alpha), a regulator of transcription that has been linked to the mediation of MCD expression by PPAR gamma, was also increased ( 3- fold). In studies also conducted 24 - 36 h after the last bout of exercise, no evidence of increased whole body insulin sensitivity or fatty acid oxidation was observed during an euglycemic hyperinsulinemic clamp. In conclusion, the concentration of malonylCoA is diminished in muscle after physical training, most likely because of PGC- 1 alpha- mediated increases in MCD expression and activity. These changes persist after the increases in AMPK activity and whole body insulin sensitivity and fatty acid oxidation, typically caused by an acute bout of exercise in healthy individuals, have dissipated.