AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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
Volume310
Issue number6
DOIs
StatePublished - Jan 1 2016

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Hypertrophy
Skeletal Muscle
Protein Isoforms
Sirolimus
Muscles
AMP-Activated Protein Kinases
Knockout Mice
Growth
Cell Enlargement
Genetically Modified Animals
Protein-Serine-Threonine Kinases
Protein Subunits
Glycogen
Transgenic Mice

All Science Journal Classification (ASJC) codes

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

Cite this

Riedl, Isabelle ; Osler, Megan E. ; Björnholm, Marie ; Egan, Brendan ; Nader, Gustavo Alberto ; Chibalin, Alexander V. ; Zierath, Juleen R. / AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload. In: American Journal of Physiology - Endocrinology and Metabolism. 2016 ; Vol. 310, No. 6. pp. E461-E472.
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AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload. / Riedl, Isabelle; Osler, Megan E.; Björnholm, Marie; Egan, Brendan; Nader, Gustavo Alberto; Chibalin, Alexander V.; Zierath, Juleen R.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 310, No. 6, 01.01.2016, p. E461-E472.

Research output: Contribution to journalArticle

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AU - Riedl, Isabelle

AU - Osler, Megan E.

AU - Björnholm, Marie

AU - Egan, Brendan

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AU - Chibalin, Alexander V.

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