AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice
AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice
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DOI：
10.1096/fj.14-266650
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发表时间：
2015-05-01
期刊：
影响因子：
4.8
通讯作者：
Wojtaszewski, Jorgen F. P.
中科院分区：
文献类型：
--
作者：
Fentz, Joachim;Kjobsted, Rasmus;Wojtaszewski, Jorgen F. P.
AMPK在收缩/运动时骨骼肌中脂肪酸（FA）氧化调节中的重要性尚不清楚。使用骨骼肌中缺乏AMPK1和-2的小鼠模型（mdKO），我们假设骨骼肌中FA的利用会受损。AMPK mdKO小鼠在喂食食物或高脂肪饮食或长时间禁食时显示正常的呼吸交换率（RER）。然而，与野生型相比，相同相对强度的体内跑步运动诱导AMPK mdKO小鼠的RER更高(WT = 0.81 +/- 0.01 (sem)；mdKO = 0.87±0.02 (sem)；P < 0.01)，表明FA利用率下降。此外，AMPK mdKO肌肉的离体收缩诱导的FA氧化受损，表明运动期间RER的增加源于骨骼肌FA氧化的减少。AMPK mdKO小鼠在收缩/运动过程中，肌肉蛋白CD36（分化簇36）和FABPpm（质膜脂肪酸结合蛋白）表达减少（约17-40%），TBC1D1 (tre2 /USP6, BUB2， cdc16结构域家族成员1)Ser（237）磷酸化完全取消，可能分别损害FA转运能力和FA转运蛋白向肌膜的转运。因此，AMPK是运动和肌肉收缩过程中正常FA代谢所必需的。Fentz， J, KjObsted， R., Birk， J. B., Jordy， A. B., Jeppesen， J., Thorsen， K., Schjerling， P., Kiens， B., Jessen， N., Viollet， B., Wojtaszewski， J. F. P. AMPK对增强小鼠体内运动期间骨骼肌脂肪酸利用至关重要。
The importance of AMPK in regulation of fatty acid (FA) oxidation in skeletal muscle with contraction/exercise is unresolved. Using a mouse model lacking both AMPK1 and -2 in skeletal muscle specifically (mdKO), we hypothesized that FA utilization would be impaired in skeletal muscle. AMPK mdKO mice displayed normal respiratory exchange ratio (RER) when fed chow or a high-fat diet, or with prolonged fasting. However, in vivo treadmill exercise at the same relative intensity induced a higher RER in AMPK mdKO mice compared to wild-type (WT = 0.81 +/- 0.01 (sem); mdKO = 0.87 +/- 0.02 (sem); P < 0.01), indicating a decreased utilization of FA. Further, ex vivo contraction-induced FA oxidation was impaired in AMPK mdKO muscle, suggesting that the increased RER during exercise originated from decreased skeletal muscle FA oxidation. A decreased muscle protein expression of CD36 (cluster of differentiation 36) and FABPpm (plasma membrane fatty acid binding protein) (by approximate to 17-40%), together with fully abolished TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) Ser(237) phosphorylation during contraction/exercise in AMPK mdKO mice, may impair FA transport capacity and FA transport protein translocation to sarcolemma, respectively. AMPK is thus required for normal FA metabolism during exercise and muscle contraction.Fentz, J., KjObsted, R., Birk, J. B., Jordy, A. B., Jeppesen, J., Thorsen, K., Schjerling, P., Kiens, B., Jessen, N., Viollet, B., Wojtaszewski, J. F. P. AMPK is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice.