AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload

Isabelle Riedl, Megan E. Osler, Marie Björnholm, Brendan Egan, Gustavo A. Nader, Alexander V. Chibalin, Juleen R. Zierath

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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 AMPKγ3 mutant-overexpressing transgenic Tg-Prkag3225Q and AMPKγ3- knockout (Prkag3‑/‑) mice, we investigated the requirement for the AMPKγ3 isoform in functional overload-induced muscle hypertrophy. Although the genetic disruption of the γ3 isoform did not impair muscle growth, control sham-operated AMPKγ3-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 AMPKrelated signaling pathways between transgenic, knockout, and wildtype 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 AMPKγ3 isoform in the regulation of skeletal muscle hypertrophy. Thus, the AMPKγ3 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.

Original languageEnglish (US)
Pages (from-to)E461-E472
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number6
StatePublished - 2016

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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