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Qin Z, Wan JJ, Sun Y, et al. ORM Promotes Skeletal Muscle Glycogen Accumulation via CCR5-Activated AMPK Pathway in Mice. Front Pharmacol. 2016;7:302doi: 10.3389/fphar.2016.00302.
Qin, Z., Wan, J. J., Sun, Y., Wang, P. Y., Su, D. F., Lei, H., & Liu, X. (2016). ORM Promotes Skeletal Muscle Glycogen Accumulation via CCR5-Activated AMPK Pathway in Mice. Frontiers in pharmacology, 7302. https://doi.org/10.3389/fphar.2016.00302
Qin, Zhen, et al. "ORM Promotes Skeletal Muscle Glycogen Accumulation via CCR5-Activated AMPK Pathway in Mice." Frontiers in pharmacology vol. 7 (2016): 302. doi: https://doi.org/10.3389/fphar.2016.00302
Qin Z, Wan JJ, Sun Y, Wang PY, Su DF, Lei H, Liu X. ORM Promotes Skeletal Muscle Glycogen Accumulation via CCR5-Activated AMPK Pathway in Mice. Front Pharmacol. 2016 Sep 13;7:302. doi: 10.3389/fphar.2016.00302. eCollection 2016. PMID: 27679573; PMCID: PMC5020064.
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Front Pharmacol. 2016 Sep 13;7:302. doi: 10.3389/fphar.2016.00302. eCollection 2016.

ORM Promotes Skeletal Muscle Glycogen Accumulation via CCR5-Activated AMPK Pathway in Mice.

Frontiers in pharmacology

Zhen Qin, Jing-Jing Wan, Yang Sun, Peng-Yuan Wang, Ding-Feng Su, Hong Lei, Xia Liu

Affiliations

  1. Department of Pharmacology, School of Pharmacy, Second Military Medical University Shanghai, China.

PMID: 27679573 PMCID: PMC5020064 DOI: 10.3389/fphar.2016.00302

Abstract

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., 2016). 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.

Keywords: AMPK; CCR5; glycogen; orosomucoid; skeletal muscle

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