Growth factor-dependent and independent regulation of skeletal muscle mass - Is IGF-1 necessary for skeletal muscle hypertrophy? -

Skeletal muscle, the most abundant tissue in the body, plays vital roles in locomotion and metabolism. Understanding the cellular processes that govern regulation of muscle mass and function represents an essential step in the development of therapeutic strategies for muscular disorders. Myostatin, a member of the TGF-β family, has been identified as a negative regulator of muscle development. Indeed, its inhibition induces an extensive skeletal muscle hypertrophy requiring the activation of Smad 1/5/8 and the Insulin/IGF-I signaling pathway, but whether other molecular mechanisms are involved in this process remains to be determined. Using transcriptomic data from various Myostatin inhibition models, we identified Pak1 as a potential mediator of Myostatin action on skeletal muscle mass. Our results show that muscle PAK1 levels are systematically increased in response to Myostatin inhibition, parallel to skeletal muscle mass, regardless of the Myostatin inhibition model. Using Pak1 knockout mice, we investigated the role of Pak1 in the skeletal muscle hypertrophy induced by different approaches of Myostatin inhibition. Our findings show that Pak1 deletion does not impede the skeletal muscle hypertrophy magnitude in response to Myostatin inhibition. Therefore, Pak1 is permissive for the skeletal muscle mass increase caused by Myostatin inhibition.

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Recent advances in understanding resistance exercise training-induced skeletal muscle hypertrophy in humans

F1000Research ◽

10.12688/f1000research.21588.1 ◽

2020 ◽

Vol 9 ◽

pp. 141 ◽

Cited By ~ 3

Author(s):

Sophie Joanisse ◽

Changhyun Lim ◽

James McKendry ◽

Jonathan C. Mcleod ◽

Tanner Stokes ◽

...

Keyword(s):

Skeletal Muscle ◽

Resistance Exercise ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Hypertrophy ◽

Resistance Exercise Training ◽

Skeletal Muscle Hypertrophy ◽

Recent Advances ◽

Development And Utilization ◽

Exercise Induced

Skeletal muscle plays a pivotal role in the maintenance of physical and metabolic health and, critically, mobility. Accordingly, strategies focused on increasing the quality and quantity of skeletal muscle are relevant, and resistance exercise is foundational to the process of functional hypertrophy. Much of our current understanding of skeletal muscle hypertrophy can be attributed to the development and utilization of stable isotopically labeled tracers. We know that resistance exercise and sufficient protein intake act synergistically and provide the most effective stimuli to enhance skeletal muscle mass; however, the molecular intricacies that underpin the tremendous response variability to resistance exercise-induced hypertrophy are complex. The purpose of this review is to discuss recent studies with the aim of shedding light on key regulatory mechanisms that dictate hypertrophic gains in skeletal muscle mass. We also aim to provide a brief up-to-date summary of the recent advances in our understanding of skeletal muscle hypertrophy in response to resistance training in humans.

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Role of IGF-I in follistatin-induced skeletal muscle hypertrophy

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00098.2015 ◽

2015 ◽

Vol 309 (6) ◽

pp. E557-E567 ◽

Cited By ~ 16

Author(s):

Caroline Barbé ◽

Stéphanie Kalista ◽

Audrey Loumaye ◽

Olli Ritvos ◽

Pascale Lause ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Hypertrophy ◽

Muscle Growth ◽

Skeletal Muscle Hypertrophy ◽

Low Concentrations ◽

Igf I

Follistatin, a physiological inhibitor of myostatin, induces a dramatic increase in skeletal muscle mass, requiring the type 1 IGF-I receptor/Akt/mTOR pathway. The aim of the present study was to investigate the role of IGF-I and insulin, two ligands of the IGF-I receptor, in the follistatin hypertrophic action on skeletal muscle. In a first step, we showed that follistatin increases muscle mass while being associated with a downregulation of muscle IGF-I expression. In addition, follistatin retained its full hypertrophic effect toward muscle in hypophysectomized animals despite very low concentrations of circulating and muscle IGF-I. Furthermore, follistatin did not increase muscle sensitivity to IGF-I in stimulating phosphorylation of Akt but, surprisingly, decreased it once hypertrophy was present. Taken together, these observations indicate that increased muscle IGF-I production or sensitivity does not contribute to the muscle hypertrophy caused by follistatin. Unlike low IGF-I, low insulin, as obtained by streptozotocin injection, attenuated the hypertrophic action of follistatin on skeletal muscle. Moreover, the full anabolic response to follistatin was restored in this condition by insulin but also by IGF-I infusion. Therefore, follistatin-induced muscle hypertrophy requires the activation of the insulin/IGF-I pathway by either insulin or IGF-I. When insulin or IGF-I alone is missing, follistatin retains its full anabolic effect, but when both are deficient, as in streptozotocin-treated animals, follistatin fails to stimulate muscle growth.

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Protein Intake and Exercise-Induced Skeletal Muscle Hypertrophy: An Update

Nutrients ◽

10.3390/nu12072023 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2023

Author(s):

Louise Deldicque

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Protein Intake ◽

Skeletal Muscle Mass ◽

Muscle Hypertrophy ◽

Sport Performance ◽

Skeletal Muscle Hypertrophy ◽

Exercise Induced ◽

Net Protein

Skeletal muscle mass is critical for sport performance and in many pathological conditions. The combination of protein intake and resistance exercise is the most efficient strategy to promote skeletal muscle hypertrophy and remodeling. However, to be really efficient, certain conditions need to be considered. The amount, type and source of proteins do all matter as well as the timing of ingestion and spreading over the whole day. Optimizing those conditions favor a positive net protein balance, which in the long term, may result in muscle mass accretion. Last but not least, it is also essential to take the nutritional status and the exercise training load into consideration when looking for maintenance or gain of skeletal muscle mass.

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Faculty Opinions recommendation of Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727746955.793533652 ◽

2017 ◽

Author(s):

Sakae Tanaka

Keyword(s):

Skeletal Muscle ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Wasting ◽

Fibroblast Growth ◽

Fibroblast Growth Factor 19

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Akt1 deficiency diminishes skeletal muscle hypertrophy by reducing satellite cell proliferation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00336.2017 ◽

2018 ◽

Vol 314 (5) ◽

pp. R741-R751 ◽

Cited By ~ 11

Author(s):

Nobuki Moriya ◽

Mitsunori Miyazaki

Keyword(s):

Skeletal Muscle ◽

Cell Proliferation ◽

Protein Synthesis ◽

Satellite Cell ◽

Muscle Mass ◽

Satellite Cells ◽

Muscle Hypertrophy ◽

Mtor Signaling ◽

Skeletal Muscle Hypertrophy ◽

Satellite Cell Proliferation

Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate. In this study, female germline Akt1 knockout (KO) mice were used to examine whether Akt1 deficiency attenuates load-induced skeletal muscle hypertrophy through suppressing mTOR-dependent signaling and satellite cell proliferation. Akt1 KO mice showed a blunted hypertrophic response of skeletal muscle, with a diminished rate of satellite cell proliferation following mechanical overload. In contrast, Akt1 deficiency did not affect the load-induced activation of mTOR signaling and the subsequent enhanced rate of protein synthesis in skeletal muscle. These observations suggest that the load-induced activation of mTOR signaling occurs independently of Akt1 regulation and that Akt1 plays a critical role in regulating satellite cell proliferation during load-induced muscle hypertrophy.

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Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice

Nature Medicine ◽

10.1038/nm.4363 ◽

2017 ◽

Vol 23 (8) ◽

pp. 990-996 ◽

Cited By ~ 61

Author(s):

Bérengère Benoit ◽

Emmanuelle Meugnier ◽

Martina Castelli ◽

Stéphanie Chanon ◽

Aurélie Vieille-Marchiset ◽

...

Keyword(s):

Skeletal Muscle ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Wasting ◽

Fibroblast Growth ◽

Fibroblast Growth Factor 19

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Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load

Scientific Reports ◽

10.1038/s41598-021-83098-z ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Naoki Kuramoto ◽

Kazuhiro Nomura ◽

Daisuke Kohno ◽

Tadahiro Kitamura ◽

Gerard Karsenty ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Muscle Hypertrophy ◽

Mechanical Load ◽

Static Condition ◽

Ribosomal Protein S6 ◽

Pi3k Signaling Pathway ◽

Induced Changes

AbstractPhosphatidylinositol 3-kinase (PI3K) plays an important role in protein metabolism and cell growth. We here show that mice (M-PDK1KO mice) with skeletal muscle–specific deficiency of 3′-phosphoinositide–dependent kinase 1 (PDK1), a key component of PI3K signaling pathway, manifest a reduced skeletal muscle mass under the static condition as well as impairment of mechanical load–induced muscle hypertrophy. Whereas mechanical load-induced changes in gene expression were not affected, the phosphorylation of ribosomal protein S6 kinase (S6K) and S6 induced by mechanical load was attenuated in skeletal muscle of M-PDK1KO mice, suggesting that PDK1 regulates muscle hypertrophy not through changes in gene expression but through stimulation of kinase cascades such as the S6K-S6 axis, which plays a key role in protein synthesis. Administration of the β2-adrenergic receptor (AR) agonist clenbuterol activated the S6K-S6 axis in skeletal muscle and induced muscle hypertrophy in mice. These effects of clenbuterol were attenuated in M-PDK1KO mice, and mechanical load–induced activation of the S6K-S6 axis and muscle hypertrophy were inhibited in mice with skeletal muscle–specific deficiency of β2-AR. Our results suggest that PDK1 regulates skeletal muscle mass under the static condition and that it contributes to mechanical load–induced muscle hypertrophy, at least in part by mediating signaling from β2-AR.

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Expression of fibroblast growth factor family during postnatal skeletal muscle hypertrophy

Journal of Applied Physiology ◽

10.1152/jappl.1999.86.1.313 ◽

1999 ◽

Vol 86 (1) ◽

pp. 313-319 ◽

Cited By ~ 24

Author(s):

Pamela Mitchell ◽

Tom Steenstrup ◽

Kevin Hannon

Keyword(s):

Skeletal Muscle ◽

Growth Factor ◽

Mrna Expression ◽

Fibroblast Growth Factor ◽

Muscle Hypertrophy ◽

Protein Localization ◽

Growth Factor Receptor ◽

Fibroblast Growth ◽

Skeletal Muscle Hypertrophy ◽

Differential Expression Pattern

The potential role of the fibroblast growth factor (FGF) family during stretch-induced postnatal skeletal muscle hypertrophy was analyzed by using an avian wing-weighting model. After 2 or 11 days of weighted stretch, anterior latissimus dorsi (ALD) muscles were, on average, 34 ( P < 0.01) and 85% ( P < 0.01) larger, respectively, than unweighted ALD control muscles. By using quantitative RT-PCR, FGF-1 mRNA expression was found to be significantly decreased in ALD muscles stretched for 2 or 11 days. In contrast, FGF-4 and FGF-10 mRNA expression was significantly increased 2 days after initiation of stretch. FGF-2, FGF-10, fibroblast growth factor receptor 1, and FREK mRNA expression was significantly increased at 11 days poststretch. Increases in FGF-2 and FGF-4 protein could be detected throughout the myofiber periphery after 11 days of stretch. On a cellular level, FGF-2 and FGF-4 proteins were differentially localized. This differential expression pattern and protein localization of the FGF family in response to stretch-induced hypertrophy suggest distinct roles for individual FGFs during the postnatal hypertrophy process.

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