scholarly journals Signaling Pathways that Mediate Skeletal Muscle Hypertrophy: Effects of Exercise Training

10.5772/51087 ◽  
2012 ◽  
Author(s):  
Tiago Fernandes ◽  
rsula P.R. ◽  
Stphano F.S. ◽  
Clber R. ◽  
Edilamar M.
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Signaling Pathways ◽  
Muscle Hypertrophy ◽  
Skeletal Muscle Hypertrophy

scholarly journals AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload

2016 ◽  
Vol 310 (6) ◽  
pp. E461-E472 ◽  
Author(s):  
Isabelle Riedl ◽  
Megan E. Osler ◽  
Marie Björnholm ◽  
Brendan Egan ◽  
Gustavo A. Nader ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Muscle Hypertrophy ◽  
Muscle Growth ◽  
Mammalian Target Of Rapamycin ◽  
Growth Control ◽  
Mass Gain ◽  
Mtor Signaling ◽  
Wild Type ◽  
Skeletal Muscle Hypertrophy

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.

scholarly journals Elevated myonuclear density during skeletal muscle hypertrophy in response to training is reversed during detraining

2019 ◽  
Vol 316 (5) ◽  
pp. C649-C654 ◽  
Author(s):  
Cory M. Dungan ◽  
Kevin A. Murach ◽  
Kaitlyn K. Frick ◽  
Savannah R. Jones ◽  
Samuel E. Crow ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Muscle Hypertrophy ◽  
Muscle Power ◽  
Wheel Running ◽  
Future Research ◽  
Plantaris Muscle ◽  
Memory Mechanism ◽  
Skeletal Muscle Hypertrophy ◽  
Muscle Memory

Myonuclei gained during exercise-induced skeletal muscle hypertrophy may be long-lasting and could facilitate future muscle adaptability after deconditioning, a concept colloquially termed “muscle memory.” The evidence for this is limited, mostly due to the lack of a murine exercise-training paradigm that is nonsurgical and reversible. To address this limitation, we developed a novel progressive weighted-wheel-running (PoWeR) model of murine exercise training to test whether myonuclei gained during exercise persist after detraining. We hypothesized that myonuclei acquired during training-induced hypertrophy would remain following loss of muscle mass with detraining. Singly housed female C57BL/6J mice performed 8 wk of PoWeR, while another group performed 8 wk of PoWeR followed by 12 wk of detraining. Age-matched sedentary cage-dwelling mice served as untrained controls. Eight weeks of PoWeR yielded significant plantaris muscle fiber hypertrophy, a shift to a more oxidative phenotype, and greater myonuclear density than untrained mice. After 12 wk of detraining, the plantaris muscle returned to an untrained phenotype with fewer myonuclei. A finding of fewer myonuclei simultaneously with plantaris deconditioning argues against a muscle memory mechanism mediated by elevated myonuclear density in primarily fast-twitch muscle. PoWeR is a novel, practical, and easy-to-deploy approach for eliciting robust hypertrophy in mice, and our findings can inform future research on the mechanisms underlying skeletal muscle adaptive potential and muscle memory.

scholarly journals Retraction Note: Alpha-ketoglutarate promotes skeletal muscle hypertrophy and protein synthesis through Akt/mTOR signaling pathways

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xingcai Cai ◽  
Canjun Zhu ◽  
Yaqiong Xu ◽  
Yuanyuan Jing ◽  
Yexian Yuan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Signaling Pathways ◽  
Muscle Hypertrophy ◽  
Mtor Signaling ◽  
Link Type ◽  
Skeletal Muscle Hypertrophy

Editor's Note: this Article has been retracted; the Retraction Note is available at https://www.nature.com/articles/s41598-020-72330-x

Muscle-specific overexpression of the type 1 IGF receptor results in myoblast-independent muscle hypertrophy via PI3K, and not calcineurin, signaling

2007 ◽  
Vol 293 (6) ◽  
pp. E1538-E1551 ◽  
Author(s):  
LeBris S. Quinn ◽  
Barbara G. Anderson ◽  
Stephen R. Plymate
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Muscle Hypertrophy ◽  
Dependent Manner ◽  
Skeletal Muscle Hypertrophy ◽  
Igf Receptor ◽  
Myotube Hypertrophy ◽  
Calcineurin Signaling ◽  
Stimulation Of

The insulin-like growth factors (IGF-I and IGF-II), working through the type 1 IGF receptor (IGF-1R), are key mediators of skeletal muscle fiber growth and hypertrophy. These processes are largely dependent on stimulation of proliferation and differentiation of muscle precursor cells, termed myoblasts. It has not been rigorously determined whether the IGFs can also mediate skeletal muscle hypertrophy in a myoblast-independent fashion. Similarly, although the phosphatidylinositol 3-kinase (PI3K) and calcineurin signaling pathways have been implicated in skeletal muscle hypertrophy, these pathways are also involved in skeletal myoblast differentiation. To determine whether the IGFs can stimulate skeletal muscle hypertrophy in a myoblast-independent fashion, we developed and validated a retroviral expression vector that mediated overexpression of the human IGF-1R in rat L6 skeletal myotubes (immature muscle fibers), but not in myoblasts. L6 myotubes transduced with this vector accumulated significantly higher amounts of myofibrillar proteins, in a ligand- and receptor-dependent manner, than controls and demonstrated significantly increased rates of protein synthesis. Stimulation of myotube hypertrophy was independent of myoblast contributions, inasmuch as these cultures did not exhibit increased levels of myoblast proliferation or differentiation. Experiments with PI3K and calcineurin inhibitors indicated that myoblast-independent myotube hypertrophy was mediated by PI3K, but not calcineurin, signaling. This study demonstrates that IGF can mediate skeletal muscle hypertrophy in a myoblast-independent fashion and suggests that muscle-specific overexpression of the IGF-1R or stimulation of its signaling pathways could be used to develop strategies to ameliorate muscle wasting without stimulating proliferative pathways leading to carcinogenesis or other pathological sequelae.

Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model

2012 ◽  
Vol 302 (5) ◽  
pp. R643-R654 ◽  
Author(s):  
Thomas Chaillou ◽  
Nathalie Koulmann ◽  
Nadine Simler ◽  
Adélie Meunier ◽  
Bernard Serrurier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Muscle Hypertrophy ◽  
Molecular Mechanisms ◽  
Muscle Growth ◽  
Female Rats ◽  
Mrna Levels ◽  
Hypertrophic Response ◽  
Protein Levels ◽  
Skeletal Muscle Hypertrophy

Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes). Hypoxia minimized the Ov-induced hypertrophy at days 5 and 12 but did not affect the hypertrophic response measured at day 56. Hypoxia early reduced the phosphorylation levels of mTOR and its downstream targets P70S6K and rpS6, but it did not affect the phosphorylation levels of Akt and 4E-BP1, in Ov muscles. The role played by specific inhibitors of mTOR, such as AMPK and hypoxia-induced factors (i.e., REDD1 and BNIP-3) was studied. REDD1 protein levels were reduced by overload and were not affected by hypoxia in Ov muscles, whereas AMPK was not activated by hypoxia. Although hypoxia significantly increased BNIP-3 mRNA levels at day 5, protein levels remained unaffected. The mRNA levels of the two atrogenes MURF1 and MAFbx were early increased by hypoxia in Ov muscles. In conclusion, hypoxia induced a transient alteration of muscle growth in this hypertrophic model, at least partly due to a specific impairment of the mTOR/P70S6K pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.

Sign in / Sign up

Export Citation Format

Share Document