AMPK gamma 3 is dispensable for skeletal muscle hypertrophy induced by functional overload

作者：Riedl Isabelle; Osler Megan E; Bjornholm Marie; Egan Brendan; Nader Gustavo A; Chibalin Alexander V; Zierath Juleen R^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2016, 310(6): E461-E472.

DOI：10.1152/ajpendo.00387.2015

• AMP-activated protein kinase-gamma(3)

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 AMPK gamma 3 mutant-overexpressing transgenic Tg-Prkag3225Q and AMPK gamma 3-knockout (Prkag3(-/-)) mice, we investigated the requirement for the AMPK gamma 3 isoform in functional overload-induced muscle hypertrophy. Although the genetic disruption of the gamma 3 isoform did not impair muscle growth, control sham-operated AMPK gamma 3-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 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 AMPK gamma 3 isoform in the regulation of skeletal muscle hypertrophy. Thus, the AMPK gamma 3 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.

• 出版日期2016-3-15