ANG II is required for optimal overload-induced skeletal muscle hypertrophy

2001 ◽  
Vol 280 (1) ◽  
pp. E150-E159 ◽  
Author(s):  
Scott E. Gordon ◽  
Bradley S. Davis ◽  
Christian J. Carlson ◽  
Frank W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Muscle Hypertrophy ◽  
Ace Inhibitor ◽  
Muscle Protein ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Surgical Ablation ◽  
Hypertrophic Response ◽  
Skeletal Muscle Hypertrophy

ANG II mediates the hypertrophic response of overloaded cardiac muscle, likely via the ANG II type 1 (AT1) receptor. To examine the potential role of ANG II in overload-induced skeletal muscle hypertrophy, plantaris and/or soleus muscle overload was produced in female Sprague-Dawley rats (225–250 g) by the bilateral surgical ablation of either the synergistic gastrocnemius muscle ( experiment 1) or both the gastrocnemius and plantaris muscles ( experiment 2). In experiment 1 ( n = 10/ group), inhibiting endogenous ANG II production by oral administration of an angiotensin-converting enzyme (ACE) inhibitor during a 28-day overloading protocol attenuated plantaris and soleus muscle hypertrophy by 57 and 96%, respectively (as measured by total muscle protein content). ACE inhibition had no effect on nonoverloaded (sham-operated) muscles. With the use of new animals ( experiment 2; n = 8/group), locally perfusing overloaded soleus muscles with exogenous ANG II (via osmotic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT1 receptor antagonist instead of an ACE inhibitor produced a 48% attenuation of overload-induced hypertrophy that could not be rescued by ANG II perfusion. Thus ANG II may be necessary for optimal overload-induced skeletal muscle hypertrophy, acting at least in part via an AT1receptor-dependent pathway.

scholarly journals Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise

2019 ◽  
Vol 126 (1) ◽  
pp. 30-43 ◽  
Author(s):  
Henning Wackerhage ◽  
Brad J. Schoenfeld ◽  
D. Lee Hamilton ◽  
Maarit Lehti ◽  
Juha J. Hulmi
Keyword(s):  
Skeletal Muscle ◽  
Resistance Exercise ◽  
Muscle Damage ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Large Body ◽  
Focal Adhesions ◽  
Indirect Evidence ◽  
Skeletal Muscle Hypertrophy ◽  
Exercise Induced

One of the most striking adaptations to exercise is the skeletal muscle hypertrophy that occurs in response to resistance exercise. A large body of work shows that a mammalian target of rapamycin complex 1 (mTORC1)-mediated increase of muscle protein synthesis is the key, but not sole, mechanism by which resistance exercise causes muscle hypertrophy. While much of the hypertrophy signaling cascade has been identified, the initiating, resistance exercise-induced and hypertrophy-stimulating stimuli have remained elusive. For the purpose of this review, we define an initiating, resistance exercise-induced and hypertrophy-stimulating signal as “hypertrophy stimulus,” and the sensor of such a signal as “hypertrophy sensor.” In this review we discuss our current knowledge of specific mechanical stimuli, damage/injury-associated and metabolic stress-associated triggers, as potential hypertrophy stimuli. Mechanical signals are the prime hypertrophy stimuli candidates, and a filamin-C-BAG3-dependent regulation of mTORC1, Hippo, and autophagy signaling is a plausible albeit still incompletely characterized hypertrophy sensor. Other candidate mechanosensing mechanisms are nuclear deformation-initiated signaling or several mechanisms related to costameres, which are the functional equivalents of focal adhesions in other cells. While exercise-induced muscle damage is probably not essential for hypertrophy, it is still unclear whether and how such muscle damage could augment a hypertrophic response. Interventions that combine blood flow restriction and especially low load resistance exercise suggest that resistance exercise-regulated metabolites could be hypertrophy stimuli, but this is based on indirect evidence and metabolite candidates are poorly characterized.

scholarly journals Exercise-Induced Muscle Damage and Hypertrophy: A Closer Look Reveals the Jury is Still Out

2018 ◽  
Author(s):  
Brad Jon Schoenfeld ◽  
Bret Contreras
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Training ◽  
Muscle Damage ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Hypertrophy ◽  
Exercise Induced

This letter is a response to the paper by Damas et al (2017) titled, “The development of skeletal muscle hypertrophy through resistance training: the role of muscle damage and muscle protein synthesis,” which, in part, endeavored to review the role of exercise-induced muscle damage on muscle hypertrophy. We feel there are a number of issues in interpretation of research and extrapolation that preclude drawing the inference expressed in the paper that muscle damage neither explains nor potentiates increases in muscle hypertrophy. The intent of our letter is not to suggest that a causal role exists between hypertrophy and microinjury. Rather, we hope to provide balance to the evidence presented and offer the opinion that the jury is still very much out as to providing answers on the topic.

Mechanical loading induces the expression of a Pol I regulon at the onset of skeletal muscle hypertrophy

2012 ◽  
Vol 302 (10) ◽  
pp. C1523-C1530 ◽  
Author(s):  
Ferdinand von Walden ◽  
Vandre Casagrande ◽  
Ann-Kristin Östlund Farrants ◽  
Gustavo A. Nader
Keyword(s):  
Skeletal Muscle ◽  
Mechanical Loading ◽  
Muscle Hypertrophy ◽  
Rrna Synthesis ◽  
Rdna Transcription ◽  
Hypertrophic Response ◽  
Skeletal Muscle Hypertrophy ◽  
Pol I ◽  
Upstream Binding Factor ◽  
Polymerase I

The main goal of the present study was to investigate the regulation of ribosomal DNA (rDNA) gene transcription at the onset of skeletal muscle hypertrophy. Mice were subjected to functional overload of the plantaris by bilateral removal of the synergist muscles. Mechanical loading resulted in muscle hypertrophy with an increase in rRNA content. rDNA transcription, as determined by 45S pre-rRNA abundance, paralleled the increase in rRNA content and was consistent with the onset of the hypertrophic response. Increased transcription and protein expression of c-Myc and its downstream polymerase I (Pol I) regulon (POL1RB, TIF-1A, PAF53, TTF1, TAF1C) was also consistent with the increase in rRNA. Similarly, factors involved in rDNA transcription, such as the upstream binding factor and the Williams syndrome transcription factor, were induced by mechanical loading in a corresponding temporal fashion. Chromatin immunoprecipitation revealed that these factors, together with Pol I, were enriched at the rDNA promoter. This, in addition to an increase in histone H3 lysine 9 acetylation, demonstrates that mechanical loading regulates rRNA synthesis by inducing a gene expression program consisting of a Pol I regulon, together with accessory factors involved in transcription and chromatin remodeling at the rDNA promoter. Altogether, these data indicate that transcriptional and epigenetic mechanisms take place in the regulation of ribosome production at the onset of muscle hypertrophy.

scholarly journals Impaired overload-induced hypertrophy in obese Zucker rat slow-twitch skeletal muscle

2010 ◽  
Vol 108 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Satyanarayana Paturi ◽  
Anil K. Gutta ◽  
Sunil K. Kakarla ◽  
Anjaiah Katta ◽  
Eric C. Arnold ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Internal Control ◽  
Muscle Hypertrophy ◽  
Surgical Ablation ◽  
Cross Sectional ◽  
Insulin Resistant ◽  
Muscle Loading ◽  
Wet Weight ◽  
Mechanical Overload

The effect of insulin resistance (IR) on the adaptation of skeletal muscle loading is not well understood. Here we examine whether the soleus muscles of the lean Zucker (LZ) and insulin-resistant obese Zucker (OZ) rat exhibit differences in their ability to undergo muscle hypertrophy following 8 wk of mechanical overload. Four-week-old male LZ ( n = 5) and OZ ( n = 5) rats underwent unilateral surgical ablation of the gastrocnemius muscle while the contralateral hindlimb was used as an internal control. Mechanical overload increased soleus muscle wet weight (LZ 57% and OZ 33%, respectively; P < 0 .05) and average type 1 fiber cross-sectional area (LZ 32% and OZ 5%, respectively; P < 0.05) in LZ and OZ rats, while the magnitude of these increases was greater in the LZ animals ( P < 0 .05). The reduced degree of muscle hypertrophy observed in the OZ animals was associated with decreases in the ability of the OZ soleus muscle to phosphorylate p70s6kThr 389 and mTOR, while phosphorylation of p70s6kThr 389 was increased in the LZ overloaded soleus by 83% ( P < 0 .05). The amount of Tuberin/TSC2 phosphorylation, an inhibitor of mTOR, was unchanged in the LZ soleus after overload while it was increased (68.3%, P < 0.05) in OZ animals. Conversely, AMPK phosphorylation was decreased in the LZ (−22.77%, P < 0 .05) but increased (57%, P < 0 .05) in the OZ soleus with overload. Taken together, these data suggest that IR or other related comorbidities may impair the ability of the soleus to activate mTOR signaling and undergo load-induced muscle hypertrophy.

scholarly journals The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy

1996 ◽  
Vol 81 (6) ◽  
pp. 2509-2516 ◽  
Author(s):  
G. R. Adams ◽  
F. Haddad
Keyword(s):  
Skeletal Muscle ◽  
Dna Content ◽  
Time Course ◽  
Muscle Hypertrophy ◽  
Weight Ratio ◽  
Surgical Removal ◽  
Protein Accumulation ◽  
Hypertrophic Response ◽  
Skeletal Muscle Hypertrophy ◽  
Strong Positive Relationship

Adams, G. R., and F. Haddad. The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy. J. Appl. Physiol. 81(6): 2509–2516, 1996.—Insulin-like growth factor-1 (IGF-1) is known to have anabolic effects on skeletal muscle cells. This study examined the time course of muscle hypertrophy and associated IGF-1 peptide and mRNA expression. Data were collected at 3, 7, 14, and 28 days after surgical removal of synergistic muscles of both normal and hypophysectomized (HX) animals. Overloading increased the plantaris (Plant) mass, myofiber size, and protein-to-body weight ratio in both groups (normal and HX; P < 0.05). Muscle IGF-1 peptide levels peaked at 3 (normal) and 7 (HX) days of overloading with maximum 4.1-fold (normal) and 6.2-fold (HX) increases. Increases in muscle IGF-1 preceded the hypertrophic response. Total DNA content of the overloaded Plant increased in both groups. There was a strong positive relationship between IGF-1 peptide and DNA content in the overloaded Plant from both groups. These results indicate that 1) the muscles from rats with both normal and severely depressed systemic levels of IGF-1 respond to functional overload with an increase in local IGF-1 expression and 2) this elevated IGF-1 may be contributing to the hypertrophy response, possibly via the mobilization of satellite cells to provide increases in muscle DNA.

scholarly journals A Phosphatidylinositol 3-Kinase/Protein Kinase B-independent Activation of Mammalian Target of Rapamycin Signaling Is Sufficient to Induce Skeletal Muscle Hypertrophy

2010 ◽  
Vol 21 (18) ◽  
pp. 3258-3268 ◽  
Author(s):  
Craig A. Goodman ◽  
Man Hing Miu ◽  
John W. Frey ◽  
Danielle M. Mabrey ◽  
Hannah C. Lincoln ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Sensitive Element ◽  
Muscle Hypertrophy ◽  
Kinase Activity ◽  
Protein Kinase B ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Phosphatidylinositol 3 Kinase ◽  
Hypertrophic Response ◽  
Skeletal Muscle Hypertrophy

It has been widely proposed that signaling by mammalian target of rapamycin (mTOR) is both necessary and sufficient for the induction of skeletal muscle hypertrophy. Evidence for this hypothesis is largely based on studies that used stimuli that activate mTOR via a phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB)-dependent mechanism. However, the stimulation of signaling by PI3K/PKB also can activate several mTOR-independent growth-promoting events; thus, it is not clear whether signaling by mTOR is permissive, or sufficient, for the induction of hypertrophy. Furthermore, the presumed role of mTOR in hypertrophy is derived from studies that used rapamycin to inhibit mTOR; yet, there is very little direct evidence that mTOR is the rapamycin-sensitive element that confers the hypertrophic response. In this study, we determined that, in skeletal muscle, overexpression of Rheb stimulates a PI3K/PKB-independent activation of mTOR signaling, and this is sufficient for the induction of a rapamycin-sensitive hypertrophic response. Transgenic mice with muscle specific expression of various mTOR mutants also were used to demonstrate that mTOR is the rapamycin-sensitive element that conferred the hypertrophic response and that the kinase activity of mTOR is necessary for this event. Combined, these results provide direct genetic evidence that a PI3K/PKB-independent activation of mTOR signaling is sufficient to induce hypertrophy. In summary, overexpression of Rheb activates mTOR signaling via a PI3K/PKB-independent mechanism and is sufficient to induce skeletal muscle hypertrophy. The hypertrophic effects of Rheb are driven through a rapamycin-sensitive (RS) mechanism, mTOR is the RS element that confers the hypertrophy, and the kinase activity of mTOR is necessary for this event.

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