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Publication : AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload.

First Author  Riedl I Year  2016
Journal  Am J Physiol Endocrinol Metab Volume  310
Issue  6 Pages  E461-72
PubMed ID  26758685 Mgi Jnum  J:236129
Mgi Id  MGI:5804750 Doi  10.1152/ajpendo.00387.2015
Citation  Riedl I, et al. (2016) AMPKgamma3 is dispensable for skeletal muscle hypertrophy induced by functional overload. Am J Physiol Endocrinol Metab 310(6):E461-72
abstractText  Mechanisms regulating skeletal muscle growth involve a balance between the activity of serine/threonine protein kinases, including the mammalian target of rapamycin (mTOR) and 5'-AMP-activated protein kinase (AMPK). The contribution of different AMPK subunits to the regulation of cell growth size remains inadequately characterized. Using AMPKgamma3 mutant-overexpressing transgenic Tg-Prkag3(225Q) and AMPKgamma3-knockout (Prkag3(-/-)) mice, we investigated the requirement for the AMPKgamma3 isoform in functional overload-induced muscle hypertrophy. Although the genetic disruption of the gamma3 isoform did not impair muscle growth, control sham-operated AMPKgamma3-transgenic mice displayed heavier plantaris muscles in response to overload hypertrophy and underwent smaller mass gain and lower Igf1 expression compared with wild-type littermates. The mTOR signaling pathway was upregulated with functional overload but unchanged between genetically modified animals and wild-type littermates. Differences in AMPK-related signaling pathways between transgenic, knockout, and wild-type mice did not impact muscle hypertrophy. Glycogen content was increased following overload in wild-type mice. In conclusion, our functional, transcriptional, and signaling data provide evidence against the involvement of the AMPKgamma3 isoform in the regulation of skeletal muscle hypertrophy. Thus, the AMPKgamma3 isoform is dispensable for functional overload-induced muscle growth. Mechanical loading can override signaling pathways that act as negative effectors of mTOR signaling and consequently promote skeletal muscle hypertrophy.
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