Hypertrophy of Rat Skeletal Muscle Is Associated with Increased SIRT1/Akt/mTOR/S6 and Suppressed Sestrin2/SIRT3/FOXO1 Levels

Despite the intensive investigation of the molecular mechanism of skeletal muscle hypertrophy, the underlying signaling processes are not completely understood. Therefore, we used an overload model, in which the main synergist muscles (gastrocnemius, soleus) of the plantaris muscle were surgically removed, to cause a significant overload in the remaining plantaris muscle of 8-month-old Wistar male rats. SIRT1-associated pro-anabolic, pro-catabolic molecular signaling pathways, NAD and H2S levels of this overload-induced hypertrophy were studied. Fourteen days of overload resulted in a significant 43% (p < 0.01) increase in the mass of plantaris muscle compared to sham operated animals. Cystathionine-β-synthase (CBS) activities and bioavailable H2S levels were not modified by overload. On the other hand, overload-induced hypertrophy of skeletal muscle was associated with increased SIRT1 (p < 0.01), Akt (p < 0.01), mTOR, S6 (p < 0.01) and suppressed sestrin 2 levels (p < 0.01), which are mostly responsible for anabolic signaling. Decreased FOXO1 and SIRT3 signaling (p < 0.01) suggest downregulation of protein breakdown and mitophagy. Decreased levels of NAD+, sestrin2, OGG1 (p < 0.01) indicate that the redox milieu of skeletal muscle after 14 days of overloading is reduced. The present investigation revealed novel cellular interactions that regulate anabolic and catabolic processes in the hypertrophy of skeletal muscle.

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Androgen cytosol binding during compensatory overload-induced skeletal muscle hypertrophy

Canadian Journal of Biochemistry and Cell Biology ◽

10.1139/o85-051 ◽

1985 ◽

Vol 63 (5) ◽

pp. 348-354 ◽

Cited By ~ 13

Author(s):

R. C. Hickson ◽

T. T. Kurowski ◽

T. M. Galassi ◽

D. G. Daniels ◽

R. J. Chatterton Jr.

Keyword(s):

Skeletal Muscle ◽

Muscle Hypertrophy ◽

Glucocorticoid Receptors ◽

Male Rats ◽

Control Group ◽

Binding Model ◽

Sequence Of Events ◽

Skeletal Muscle Hypertrophy ◽

High Concentrations ◽

The Individual

This study was undertaken to evaluate whether the increased androgen cytosol binding is an early or later event in the sequence of skeletal muscle hypertrophy induced by surgical overload. Following removal of the synergistic gastrocnemius and soleus muscles, plantaris muscle weights of overloaded hypophysectomized male rats were heavier than those in the controls by 29% at 2 days, 41% at 7 days, 38% at 14 days, and 47% at 35 days. Androgen cytosol receptor binding capacities (femtomoles per milligram protein), determined using a synthetic androgen, [3H]methyltrienolone (R1881), were higher than observed in muscles of controls at all points of muscle enlargement. At high concentrations of labeled ligand, Scatchard analyses became nonlinear and were resolved using a two-component binding model. Receptor capacity of the higher affinity "androgenic component" for methyltrienolone binding in plantaris muscles was lower at 2 days but 60–80% higher at 7, 14, and 35 days in the hypertrophied group than in the control group. The lower affinity "glucocorticoid component" was higher in the overloaded group at all points following surgery. Several glucocorticoids and estradiol-17β competed equally with androgens for methyltrienolone binding. However, when cytosol s were incubated with triamcinolone acetonide to block methyltrienolone binding to glucocorticoid receptors, the androgenic component was highly specific for androgens. These results show that total [3H]methyltrienolone cytosol concentrations increased in parallel with the muscle hypertrophy, yet the individual components of methyltrienolone binding attained greater concentrations in overloaded muscles by an apparently different sequence of events.

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Induction of Plasma Insulin by Dietary Sucrose Promotes Rat Skeletal Muscle Hypertrophy Under High-Protein Diets

Medicine & Science in Sports & Exercise ◽

10.1097/00005768-200405001-01549 ◽

2004 ◽

Vol 36 (Supplement) ◽

pp. S323

Author(s):

Hongsun Song ◽

Koichi Nakazato ◽

Hiroyuki Nakajima

Keyword(s):

Skeletal Muscle ◽

Plasma Insulin ◽

Muscle Hypertrophy ◽

High Protein ◽

Rat Skeletal Muscle ◽

Skeletal Muscle Hypertrophy ◽

High Protein Diets ◽

Protein Diets

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

AJP Cell Physiology ◽

10.1152/ajpcell.00050.2019 ◽

2019 ◽

Vol 316 (5) ◽

pp. C649-C654 ◽

Cited By ~ 18

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.

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Regulation of myosin heavy-chain gene expression during skeletal-muscle hypertrophy

Biochemical Journal ◽

10.1042/bj2570691 ◽

1989 ◽

Vol 257 (3) ◽

pp. 691-698 ◽

Cited By ~ 37

Author(s):

M Periasamy ◽

P Gregory ◽

B J Martin ◽

W S Stirewalt

Keyword(s):

Skeletal Muscle ◽

Muscle Hypertrophy ◽

Compensatory Hypertrophy ◽

Chain Gene ◽

Mrna Levels ◽

Muscle Adaptation ◽

Myosin Heavy Chain Gene ◽

Rat Skeletal Muscle ◽

Skeletal Muscle Hypertrophy ◽

Myosin Isoenzymes

Changes in the myosin phenotype of differentiated muscle are a prominent feature of the adaptation of the tissue to a variety of physiological stimuli. In the present study the molecular basis of changes in the proportion of myosin isoenzymes in rat skeletal muscle which occur during compensatory hypertrophy caused by the combined removal of synergist muscles and spontaneous running exercise was investigated. The relative amounts of sarcomeric myosin heavy (MHC)- and light (MLC)-chain mRNAs in the plantaris (fast) and soleus (slow) muscles from rats was assessed with cDNA probes specific for different MHC and MLC genes. Changes in the proportion of specific MHC mRNA levels were in the same direction as, and of similar magnitude to, changes in the proportion of myosin isoenzymes encoded for by the mRNAs. No significant changes in the proportion of MLC proteins or mRNA were detected. However, high levels of MLC3 mRNA were measured in both normal and hypertrophied soleus muscles which contained only trace amounts of MLC3 protein. Small amounts of embryonic and neonatal MHC mRNAs were induced in both muscles during hypertrophy. We conclude that the change in the pattern of myosin isoenzymes during skeletal-muscle adaptation to work overload is a consequence of changes in specific MHC mRNA levels.

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Induction of Plasma Insulin by Dietary Sucrose Promotes Rat Skeletal Muscle Hypertrophy Under High-Protein Diets

Medicine & Science in Sports & Exercise ◽

10.1249/00005768-200405001-01549 ◽

2004 ◽

Vol 36 (Supplement) ◽

pp. S323

Author(s):

Hongsun Song ◽

Koichi Nakazato ◽

Hiroyuki Nakajima

Keyword(s):

Skeletal Muscle ◽

Plasma Insulin ◽

Muscle Hypertrophy ◽

High Protein ◽

Rat Skeletal Muscle ◽

Skeletal Muscle Hypertrophy ◽

High Protein Diets ◽

Protein Diets

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Transcriptional profiling of rat skeletal muscle hypertrophy under restriction of blood flow

Gene ◽

10.1016/j.gene.2016.09.008 ◽

2016 ◽

Vol 594 (2) ◽

pp. 229-237 ◽

Cited By ~ 3

Author(s):

Shouyu Xu ◽

Xueyun Liu ◽

Zhenhuang Chen ◽

Gaoquan Li ◽

Qin Chen ◽

...

Keyword(s):

Skeletal Muscle ◽

Blood Flow ◽

Muscle Hypertrophy ◽

Transcriptional Profiling ◽

Rat Skeletal Muscle ◽

Skeletal Muscle Hypertrophy

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Increased association of ribosomes with myofibrils during the skeletal-muscle hypertrophy induced either by the β-adrenoceptor agonist clenbuterol or by tenotomy

Biochemical Journal ◽

10.1042/bj2720831 ◽

1990 ◽

Vol 272 (3) ◽

pp. 831-833 ◽

Cited By ~ 21

Author(s):

Z Horne ◽

J Hesketh

Keyword(s):

Skeletal Muscle ◽

Muscle Hypertrophy ◽

Ribosomal Subunit ◽

Plantaris Muscle ◽

Beta Adrenoceptor ◽

Skeletal Muscle Hypertrophy ◽

Adrenoceptor Agonist

Ribosome distribution in skeletal-muscle myofibres was investigated by immunohistochemistry and microdensitometry by using anti-(60 S ribosomal subunit) antibodies. Administration of the beta-adrenoceptor agonist clenbuterol caused an increase in the staining of the myofibrillar region with this antibody relative to that found in the subsarcolemmal cytoplasm. A similar effect was observed during hypertrophy of the plantaris muscle following severance of the tendon to the gastrocnemius. The results suggest that increased association of ribosomes with the myofibrils occurs during muscle hypertrophy.

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Skeletal muscle hypertrophy in rats having growth hormone-secreting tumor

Journal of Applied Physiology ◽

10.1152/jappl.1986.61.5.1732 ◽

1986 ◽

Vol 61 (5) ◽

pp. 1732-1735 ◽

Cited By ~ 8

Author(s):

T. L. Riss ◽

J. Novakofski ◽

P. J. Bechtel

Keyword(s):

Skeletal Muscle ◽

Growth Hormone ◽

Muscle Hypertrophy ◽

Gastrocnemius Muscle ◽

Gh3 Cells ◽

Plantaris Muscle ◽

Tumor Bearing ◽

Skeletal Muscle Hypertrophy ◽

Tumor Group ◽

The Right

Plantaris muscle hypertrophy resulting from surgical ablation of the synergistic gastrocnemius muscle was compared between nontumor- and GH3 tumor-bearing rat groups (n = 8–10). GH3 cells (10(6)) were subcutaneously injected into 150-g female Wistar-Furth rats to initiate the tumor. After 17 days, the tumor-bearing rats gained 5.7 g body wt/day compared with 2.0 for the nontumor-bearing rats. The left gastrocnemius muscle was surgically removed from both nontumor and tumor groups. The gastrocnemius was removed from the tumor group after an increased growth rate was achieved. Seven days after surgery, the animals were killed and plantaris muscles were removed. The wet weight of the left plantaris muscle increased 45.6 and 44.0% over the unoperated contralateral control (right side) in the nontumor and tumor groups, respectively. The right control plantaris muscle in the tumor group was 63% heavier than the right control plantaris from the nontumor group; however, the proportion of body weight for plantaris was similar between the two groups. The effect of gastrocnemius ablation and tumor treatment on plantaris weight was additive, and the percent increase over the unoperated contralateral control side was similar between the two groups. These data demonstrate that skeletal muscle hypertrophy occurs in adult animals in which growth has been stimulated by a growth hormone-secreting tumor and could suggest that the muscle growth response caused by the tumor is operating by a mechanism different than work-induced hypertrophy.

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