title: AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload.
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-Prkag3(225Q) 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 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 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.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Riedl
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Megan E
authors.initials: ME
authors.lastname: Osler
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Marie
authors.initials: M
authors.lastname: Björnholm
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Institute for Sport and Health, School of Public Health, Physiotherapy, and Population Science, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Brendan
authors.initials: B
authors.lastname: Egan
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; and.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Nader
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden;
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Chibalin
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; and Juleen.Zierath@ki.se.
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics*; D000818:Animals; D006984:Hypertrophy / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism; D009929:Organ Size; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; C546843:mTOR protein, mouse; C526221:Prkag3 protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase-γ3