scholarly journals Akt1 deficiency diminishes skeletal muscle hypertrophy by reducing satellite cell proliferation

2018 ◽  
Vol 314 (5) ◽  
pp. R741-R751 ◽  
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.

scholarly journals Satellite cell proliferation and skeletal muscle hypertrophy

2006 ◽  
Vol 31 (6) ◽  
pp. 782-790 ◽  
Author(s):  
Gregory R. Adams
Keyword(s):  
Cell Proliferation ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Hypertrophy ◽  
Mononuclear Cells ◽  
Close Association ◽  
Critical Role ◽  
Skeletal Muscle Hypertrophy ◽  
Muscle Loading ◽  
Satellite Cell Proliferation

Satellite cells are small, mononuclear cells found in close association with striated skeletal muscles cells (myofibers). These cells appear to function as reserve myoblasts. A critical role for these cells in the process of muscle regeneration following injury has been clearly established. In that role, satellite cells have been shown to proliferate extensively. Some of the progeny of these cells then fuse with each other to form replacement myofibers, whereas others return to quiescence, thereby maintaining this reserve population. In response to injury, activated satellite cells can also fuse with damaged but viable myofibers to promote repair and regeneration. It has also been observed that satellite cells are activated during periods of significantly increased muscle loading and that some of these cells fuse with apparently undamaged myofibers as part of the hypertrophy process. The observation that the inactivation of satellite cell proliferation prevents most of the hypertrophy response to chronic increases in loading has lead to the hypothesis that a limitation to the expansion of myofiber size is imposed by the number of myonuclei present. Recent evidence suggests that a potential limitation to muscle hypertrophy, in the absence of a reserve supply of myonuclei, may be the inability to sustain increases in ribosomes, thereby limiting translational capacity.

Satellite cell proliferation and differentiation during postnatal growth of porcine skeletal muscle

2002 ◽  
Vol 282 (4) ◽  
pp. C899-C906 ◽  
Author(s):  
N. T Mesires ◽  
M. E. Doumit
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Nuclear Antigen ◽  
Positive Staining ◽  
Age Related ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Satellite Cell Proliferation

Age-related changes in satellite cell proliferation and differentiation during rapid growth of porcine skeletal muscle were examined. Satellite cells were isolated from hindlimb muscles of pigs at 1, 7, 14, and 21 wk of age (4 animals/age group). Satellite cells were separated from cellular debris by using Percoll gradient centrifugation and were adsorbed to glass coverslips for fluorescent immunostaining. Positive staining for neural cell adhesion molecule (NCAM) distinguished satellite cells from nonmyogenic cells. The proportion of NCAM-positive cells (satellite cells) in isolates decreased from 1 to 7 wk of age. Greater than 77% of NCAM-positive cells were proliferating cell nuclear antigen positive at all ages studied. Myogenin-positive satellite cells decreased from 30% at 1 wk to 14% at 7 wk of age and remained at constant levels thereafter. These data indicate that a high percentage of satellite cells remain proliferative during rapid postnatal muscle growth. The reduced proportion of myogenin-positive cells during growth may reflect a decrease in the proportion of differentiating satellite cells or accelerated incorporation of myogenin-positive cells into myofibers.

IGF-I restores satellite cell proliferative potential in immobilized old skeletal muscle

2000 ◽  
Vol 89 (4) ◽  
pp. 1365-1379 ◽  
Author(s):  
Manu V. Chakravarthy ◽  
Bradley S. Davis ◽  
Frank W. Booth
Keyword(s):  
Cell Proliferation ◽  
Satellite Cell ◽  
Muscle Mass ◽  
Satellite Cells ◽  
Gastrocnemius Muscle ◽  
Recovery Period ◽  
Proliferative Potential ◽  
Remaining Capacity ◽  
Satellite Cell Proliferation ◽  
Proliferation Potential

One of the key factors responsible for the age-associated reduction in muscle mass may be that satellite cell proliferation potential (number of doublings contained within each cell) could become rate limiting to old muscle regrowth. No studies have tested whether repeated cycles of atrophy-regrowth in aged animals deplete the remaining capacity of satellite cells to replicate or what measures can be taken to prevent this from happening. We hypothesized that there would be a pronounced loss of satellite cell proliferative potential in gastrocnemius muscles of aged rats (25- to 30-mo-old FBN rats) subjected to three cycles of atrophy by hindlimb immobilization (plaster casts) with intervening recovery periods. Our results indicated that there was a significant loss in gastrocnemius muscle mass and in the proliferative potential of the resident satellite cells after just one bout of immobilization. Neither the muscle mass nor the satellite cell proliferation potential recovered from their atrophied values after either the first 3-wk or later 9-wk recovery period. Remarkably, application of insulin-like growth factor I onto the atrophied gastrocnemius muscle for an additional 2 wk after this 9-wk recovery period rescued ∼46% of the lost muscle mass and dramatically increased proliferation potential of the satellite cells from this muscle.

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

The Molecular Responses of Skeletal Muscle Satellite Cells to Continuous Expression of IGF-1: Implications for the Rescue of Induced Muscular Atrophy in Aged Rats

2001 ◽  
Vol 11 (s1) ◽  
pp. S44-S48 ◽  
Author(s):  
Manu V. Chakravarthy ◽  
Frank W. Booth ◽  
Espen E. Spangenburg
Keyword(s):  
Skeletal Muscle ◽  
Cell Proliferation ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Molecular Mechanisms ◽  
Muscular Atrophy ◽  
Skeletal Muscle Atrophy ◽  
Molecular Evidence ◽  
Igf I ◽  
Satellite Cell Proliferation

Approximately 50% of humans older than 85 years have physical frailty due to weak skeletal muscles. This indicates a need for determining mechanisms to combat this problem. A critical cellular factor for postnatal muscle growth is a population of myogenic precursor cells called satellite cells. Given the complex process of sarcopenia, it has been postulated that, at some point in this process, a limited satellite cell proliferation potential could become rate-limiting to the regrowth of old muscles. It is conceivable that if satellite cell proliferative capacity can be maintained or enhanced with advanced age, sarcopenia could potentially be delayed or prevented. Therefore, the purposes of this paper are to describe whether IGF-I can prevent muscular atrophy induced by repeated cycles of hindlimb immobilization, increase the in vitro proliferation in satellite cells from these muscles and, if so, the molecular mechanisms by which IGF-1 mediates this increased proliferation. Our results provide evidence that IGFI can enhance aged muscle regrowth possibly through increased satellite cell proliferation. The results also suggest that IGF-I enhances satellite cell proliferation by decreasing the cell cycle inhibitor, p27Kip1, through the PI3’-K/Akt pathway. These data provide molecular evidence for IGF-I’s rescue effect upon aging-associated skeletal muscle atrophy.

Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin

2009 ◽  
Vol 297 (1) ◽  
pp. E157-E164 ◽  
Author(s):  
Hélène Gilson ◽  
Olivier Schakman ◽  
Stéphanie Kalista ◽  
Pascale Lause ◽  
Kunihiro Tsuchida ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Satellite Cell ◽  
Muscle Mass ◽  
Muscle Hypertrophy ◽  
Muscle Growth ◽  
Negative Regulator ◽  
Proliferative Capacity ◽  
Muscle Weight ◽  
Satellite Cell Proliferation

Follistatin (FS) inhibits several members of the TGF-β superfamily, including myostatin (Mstn), a negative regulator of muscle growth. Mstn inhibition by FS represents a potential therapeutic approach of muscle atrophy. The aim of our study was to investigate the mechanisms of the FS-induced muscle hypertrophy. To test the role of satellite cells in the FS effect, we used irradiation to destroy their proliferative capacity. FS overexpression increased the muscle weight by about 37% in control animals, but the increase reached only 20% in irradiated muscle, supporting the role of cell proliferation in the FS-induced hypertrophy. Surprisingly, the muscle hypertrophy caused by FS reached the same magnitude in Mstn-KO as in WT mice, suggesting that Mstn might not be the only ligand of FS involved in the regulation of muscle mass. To assess the role of activin (Act), another FS ligand, in the FS-induced hypertrophy, we electroporated FSI-I, a FS mutant that does not bind Act with high affinity. Whereas FS electroporation increased muscle weight by 32%, the muscle weight gain induced by FSI-I reached only 14%. Furthermore, in Mstn-KO mice, FSI-I overexpression failed to induce hypertrophy, in contrast to FS. Therefore, these results suggest that Act inhibition may contribute to FS-induced hypertrophy. Finally, the role of Act as a regulator of muscle mass was supported by the observation that ActA overexpression induced muscle weight loss (−15%). In conclusion, our results show that satellite cell proliferation and both Mstn and Act inhibition are involved in the FS-induced muscle hypertrophy.

scholarly journals The role of raptor in the mechanical load‐induced regulation of mTOR signaling, protein synthesis, and skeletal muscle hypertrophy

2018 ◽  
Vol 33 (3) ◽  
pp. 4021-4034 ◽  
Author(s):  
Jae-Sung You ◽  
Rachel M. Mcnally ◽  
Brittany L. Jacobs ◽  
Rachel E. Privett ◽  
David M. Gundermann ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Hypertrophy ◽  
Mechanical Load ◽  
Mtor Signaling ◽  
Signaling Protein ◽  
Skeletal Muscle Hypertrophy

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

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Xingcai Cai ◽  
Canjun Zhu ◽  
Yaqiong Xu ◽  
Yuanyuan Jing ◽  
Yexian Yuan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mtor Signaling ◽  
Skeletal Muscle Protein ◽  
Muscle Weight ◽  
Skeletal Muscle Hypertrophy ◽  
Skeletal Muscle Protein Synthesis

Abstract Skeletal muscle weight loss is accompanied by small fiber size and low protein content. Alpha-ketoglutarate (AKG) participates in protein and nitrogen metabolism. The effect of AKG on skeletal muscle hypertrophy has not yet been tested, and its underlying mechanism is yet to be determined. In this study, we demonstrated that AKG (2%) increased the gastrocnemius muscle weight and fiber diameter in mice. Our in vitro study also confirmed that AKG dose increased protein synthesis in C2C12 myotubes, which could be effectively blocked by the antagonists of Akt and mTOR. The effects of AKG on skeletal muscle protein synthesis were independent of glutamate, its metabolite. We tested the expression of GPR91 and GPR99. The result demonstrated that C2C12 cells expressed GPR91, which could be upregulated by AKG. GPR91 knockdown abolished the effect of AKG on protein synthesis but failed to inhibit protein degradation. These findings demonstrated that AKG promoted skeletal muscle hypertrophy via Akt/mTOR signaling pathway. In addition, GPR91 might be partially attributed to AKG-induced skeletal muscle protein synthesis.

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