ORM Promotes Skeletal Muscle Glycogen Accumulation via CCR5-Activated AMPK Pathway in Mice.
ORM Promotes Skeletal Muscle Glycogen Accumulation via CCR5-Activated AMPK Pathway in Mice.
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DOI：
10.3389/fphar.2016.00302
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发表时间：
2016
影响因子：
5.6
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Qin Z;Wan JJ;Sun Y;Wang PY;Su DF;Lei H;Liu X
我们之前发现，急性时相蛋白orosomucid对疲劳做出反应，激活C-C趋化因子受体5型，以增加肌肉糖原储存和增强肌肉耐力(Lei等人，)。为了探索潜在的分子机制，我们研究了AMP激活的蛋白激酶在C-C趋化因子受体5型介导的类口腔粘液作用中的作用。研究发现，Orosomid以时间和剂量依赖的方式增加骨骼肌AMP激活的蛋白激酶活性，这在很大程度上可被药物阻断或敲除C-C趋化因子受体5型所阻止。Orosomid还显著增加了肌肉糖原合成酶的去磷酸化和活性，糖原合成的限速酶。在缺乏C-C趋化因子受体5−/−或AMP激活的蛋白激酶α2−/−(骨骼肌中的主要亚型)缺陷的小鼠中，这种作用基本上是不存在的。此外，AMP激活的蛋白激酶α2的缺失消除了orosomid对疲劳和肌糖原的影响。这些结果表明，类粘蛋白可能通过C-C趋化因子受体5激活AMP激活的蛋白激酶，进而激活糖原合成酶，增加肌肉糖原，从而促进糖原储存，增强肌肉功能。
We found previously that acute phase protein orosomucoid reacts to fatigue and activates C-C chemokine receptor type 5 to increase muscle glycogen storage and enhance muscle endurance (Lei et al.,). To explore the underlying molecular mechanisms, we investigated the role of AMP-activated protein kinase, a critical fuel sensor in skeletal muscle, in C-C chemokine receptor type 5-mediated orosomucoid action. It was found orosomucoid increased skeletal muscle AMP-activated protein kinase activation in a time- and dose- dependent manner, which was largely prevented by pharmacological blocking or knockout of C-C chemokine receptor type 5. Administration of orosomucoid also significantly increased the de-phosphorylation and activity of muscle glycogen synthase, the rate-limiting enzyme for glycogen synthesis. The effect was largely absent in mice deficient in C-C chemokine receptor type 5−/− or AMP-activated protein kinase α2−/−, the predominant isoform in skeletal muscle. Moreover, deletion of AMP-activated protein kinase α2 abolished the effect of orosomucoid on fatigue and muscle glycogen. These findings indicate that orosomucoid may promote glycogen storage and enhance muscle function through C-C chemokine receptor type 5-mdiated activation of AMP-activated protein kinase, which in turn activates glycogen synthase and increases muscle glycogen.