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Calcified Tissue International Mar 2015In a mature (weight neutral) animal, an increase in muscle mass only occurs when the muscle is loaded sufficiently to cause an increase in myofibrillar protein balance.... (Review)
Review
In a mature (weight neutral) animal, an increase in muscle mass only occurs when the muscle is loaded sufficiently to cause an increase in myofibrillar protein balance. A tight relationship between muscle hypertrophy, acute increases in protein balance, and the activity of the mechanistic target of rapamycin complex 1 (mTORC1) was demonstrated 15 years ago. Since then, our understanding of the signals that regulate load-induced hypertrophy has evolved considerably. For example, we now know that mechanical load activates mTORC1 in the same way as growth factors, by moving TSC2 (a primary inhibitor of mTORC1) away from its target (the mTORC activator) Rheb. However, the kinase that phosphorylates and moves TSC2 is different in the two processes. Similarly, we have learned that a distinct pathway exists whereby amino acids activate mTORC1 by moving it to Rheb. While mTORC1 remains at the forefront of load-induced hypertrophy, the importance of other pathways that regulate muscle mass are becoming clearer. Myostatin, is best known for its control of developmental muscle size. However, new mechanisms to explain how loading regulates this process are suggesting that it could play an important role in hypertrophic muscle growth as well. Last, new mechanisms are highlighted for how β2 receptor agonists could be involved in load-induced muscle growth and why these agents are being developed as non-exercise-based therapies for muscle atrophy. Overall, the results highlight how studying the mechanism of load-induced skeletal muscle mass is leading the development of pharmaceutical interventions to promote muscle growth in those unwilling or unable to perform resistance exercise.
Topics: Animals; Humans; Hypertrophy; Muscle, Skeletal; Resistance Training
PubMed: 25359125
DOI: 10.1007/s00223-014-9925-9 -
BMC Musculoskeletal Disorders Oct 2022People with hip osteoarthritis are typically offered a combination of education and exercise to address muscle atrophy and weakness. Limited evidence exists to assess... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of a targeted resistance intervention compared to a sham intervention on gluteal muscle hypertrophy, fatty infiltration and strength in people with hip osteoarthritis: analysis of secondary outcomes from a randomised clinical trial.
BACKGROUND
People with hip osteoarthritis are typically offered a combination of education and exercise to address muscle atrophy and weakness. Limited evidence exists to assess the efficacy of exercise programs on muscle structure or function in this population. The aim of this study was to evaluate the effects of targeted resistance exercise on gluteal muscle hypertrophy and strength in people with mild-to-moderate hip osteoarthritis.
METHODS
Twenty-seven participants with radiologically confirmed hip osteoarthritis recruited from a single site of a multi-site, double-blind clinical trial were randomly allocated to receive a 12-week targeted gluteal intervention or sham intervention. Magnetic resonance imaging and hand-held dynamometry were used to determine change in gluteal muscle volume, fatty infiltration and hip muscle strength. For gluteal muscle volume and strength outcomes mixed model analyses of variance (ANOVA) were conducted. A general linear model (ANOVA) analysis with fixed effects parameter estimates was used to assess the impact of sex on gluteal muscle size and strength of the affected limb only. For muscle fat index a mixed method ANOVA was used to assess the differences between groups and over time.
RESULTS
In the targeted intervention group, gluteus minimus volume increased from baseline to post-intervention in both limbs (pooled mean difference: 0.06 cm/kg, 95% confidence interval: 0.01 to 0.11) while no change occurred in the sham group (time x group effect: P = 0.025). Gluteus medius, gluteus maximus and tensor fascia lata volume did not change significantly over time. Hip strength (abduction, adduction, flexion, extension, external and internal rotation) improved similarly in both groups (time main effect: P ≤ 0.042). There was a consistent, albeit non-significant, pattern of reduced fatty infiltration after the targeted intervention.
CONCLUSION
Targeted resistance exercise resulted in gluteus minimus hypertrophy, but improvements in hip strength occurred in both groups. Clinicians delivering hip osteoarthritis rehabilitation programs might consider implementing a targeted exercise program to attenuate disease associated changes within gluteal muscles.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry, ID: ACTRN12617000970347. Registered prospectively on 5 July 2017.
Topics: Humans; Osteoarthritis, Hip; Australia; Muscle Strength; Muscle, Skeletal; Buttocks; Hypertrophy
PubMed: 36309690
DOI: 10.1186/s12891-022-05907-4 -
Canadian Medical Association Journal Nov 1963Dysphagia associated with cricopharyngeal achalasia and pharyngeal diverticulum appears in many cases to be secondary to hypertrophy and imperfect function of the...
Dysphagia associated with cricopharyngeal achalasia and pharyngeal diverticulum appears in many cases to be secondary to hypertrophy and imperfect function of the cricopharyngeus muscle. Sutherland has recently suggested and carried out a posterior midline myotomy of the cricopharyngeus with strikingly beneficial improvement in dysphagia due to this cause. An example of cricopharyngeal achalasia, for which the Sutherland procedure has been carried out, is reported.
Topics: Bursa, Synovial; Deglutition Disorders; Dental Care; Esophageal Achalasia; Fascia; Humans; Hypertrophy; Muscles; Pharyngeal Diseases; Pharyngeal Muscles; Pharynx; Surgical Procedures, Operative; Tendons; Torso; Zenker Diverticulum
PubMed: 14079127
DOI: No ID Found -
The American Journal of Pathology Apr 2019Caveolins (CAVs) are structural proteins of caveolae that function as signaling platforms to regulate smooth muscle contraction. Loss of CAV protein expression is...
Caveolins (CAVs) are structural proteins of caveolae that function as signaling platforms to regulate smooth muscle contraction. Loss of CAV protein expression is associated with impaired contraction in obstruction-induced bladder smooth muscle (BSM) hypertrophy. In this study, microarray analysis of bladder RNA revealed down-regulation of CAV1, CAV2, and CAV3 gene transcription in BSM from models of obstructive bladder disease in mice and humans. We identified and characterized regulatory regions responsible for CAV1, CAV2, and CAV3 gene expression in mice with obstruction-induced BSM hypertrophy, and in men with benign prostatic hyperplasia. DNA affinity chromatography and chromatin immunoprecipitation assays revealed a greater increase in binding of GATA-binding factor 6 (GATA-6) and NF-κB to their cognate binding motifs on CAV1, CAV2, and CAV3 promoters in obstructed BSM relative to that observed in control BSM. Knockout of NF-κB subunits, shRNA-mediated knockdown of GATA-6, or pharmacologic inhibition of GATA-6 and NF-κB in BSM increased CAV1, CAV2, and CAV3 transcription and promoter activity. Conversely, overexpression of GATA-6 decreased CAV2 and CAV3 transcription and promoter activity. Collectively, these data provide new insight into the mechanisms by which CAV gene expression is repressed in hypertrophied BSM in obstructive bladder disease.
Topics: Aged; Animals; Biomarkers; Caveolins; GATA6 Transcription Factor; Gene Expression Profiling; Gene Expression Regulation; Humans; Hypertrophy; Male; Mice; Mice, Inbred C57BL; Middle Aged; Muscle Contraction; Muscle, Smooth; NF-kappa B; Prostatic Hyperplasia; Transcription, Genetic; Urinary Bladder Neck Obstruction
PubMed: 30707892
DOI: 10.1016/j.ajpath.2018.12.013 -
Journal of Applied Physiology... Aug 2019The decline of skeletal muscle mass during illness, injury, disuse, and aging is associated with poor health outcomes. Therefore, it is important to pursue a greater... (Review)
Review
The decline of skeletal muscle mass during illness, injury, disuse, and aging is associated with poor health outcomes. Therefore, it is important to pursue a greater understanding of the mechanisms that dictate skeletal muscle adaptation. In this review, we propose that RNA-binding proteins (RBPs) comprise a critical regulatory node in the orchestration of adaptive responses in skeletal muscle. While RBPs have broadly pleiotropic molecular functions, our discussion is constrained at the outset by observations from hibernating animals, which suggest that RBP regulation of RNA stability and its impact on translational reprogramming is a key component of skeletal muscle response to anabolic and catabolic stimuli. We discuss the limited data available on the expression and functions of RBPs in adult skeletal muscle in response to disuse, aging, and exercise. A model is proposed in which dynamic changes in RBPs play a central role in muscle adaptive processes through their differential effects on mRNA stability. While limited, the currently available data suggest that understanding how adaptive (and maladaptive) changes in the expression of RBPs regulate mRNA stability in skeletal muscle could be an informative and productive research area for finding new strategies to limit atrophy and promote hypertrophy.
Topics: Adaptation, Physiological; Animals; Exercise; Humans; Hypertrophy; Muscle, Skeletal; Muscular Atrophy; RNA, Messenger; RNA-Binding Proteins
PubMed: 31120811
DOI: 10.1152/japplphysiol.00076.2019 -
American Journal of Physiology. Heart... Sep 2017The energy starvation hypothesis proposes that maladaptive metabolic remodeling antedates, initiates, and maintains adverse contractile dysfunction in heart failure... (Review)
Review
The energy starvation hypothesis proposes that maladaptive metabolic remodeling antedates, initiates, and maintains adverse contractile dysfunction in heart failure (HF). Better understanding of the cardiac metabolic phenotype and metabolic signaling could help identify the role metabolic remodeling plays within HF and the conditions known to transition toward HF, including "pathological" hypertrophy. In this review, we discuss metabolic phenotype and metabolic signaling in the contexts of pathological hypertrophy and HF. We discuss the significance of alterations in energy supply (substrate utilization, oxidative capacity, and phosphotransfer) and energy sensing using observations from human and animal disease models and models of manipulated energy supply/sensing. We aim to provide ways of thinking about metabolic remodeling that center around metabolic flexibility, capacity (reserve), and efficiency rather than around particular substrate preferences or transcriptomic profiles. We show that maladaptive metabolic remodeling takes multiple forms across multiple energy-handling domains. We suggest that lack of metabolic flexibility and reserve (substrate, oxidative, and phosphotransfer) represents a final common denominator ultimately compromising efficiency and contractile reserve in stressful contexts.
Topics: Adaptation, Physiological; Animals; Cardiomegaly; Disease Progression; Energy Metabolism; Heart Failure; Humans; Myocardium; Phenotype
PubMed: 28646030
DOI: 10.1152/ajpheart.00731.2016 -
Revista Da Associacao Medica Brasileira... Feb 2017The aim was to evaluate the effectiveness of the experimental synergists muscle ablation model to promote muscle hypertrophy, determine the period of greatest... (Review)
Review
OBJECTIVE:
The aim was to evaluate the effectiveness of the experimental synergists muscle ablation model to promote muscle hypertrophy, determine the period of greatest hypertrophy and its influence on muscle fiber types and determine differences in bilateral and unilateral removal to reduce the number of animals used in this model.
METHOD:
Following the application of the eligibility criteria for the mechanical overload of the plantar muscle in rats, nineteen papers were included in the review.
RESULTS:
The results reveal a greatest hypertrophy occurring between days 12 and 15, and based on the findings, synergist muscle ablation is an efficient model for achieving rapid hypertrophy and the contralateral limb can be used as there was no difference between unilateral and bilateral surgery, which reduces the number of animals used in this model.
CONCLUSION:
This model differs from other overload models (exercise and training) regarding the characteristics involved in the hypertrophy process (acute) and result in a chronic muscle adaptation with selective regulation and modification of fast-twitch fibers in skeletal muscle. This is an efficient and rapid model for compensatory hypertrophy.
Topics: Ablation Techniques; Animals; Hypertrophy; Models, Animal; Muscle Contraction; Muscle Denervation; Muscle, Skeletal; Rats; Tendons
PubMed: 28355378
DOI: 10.1590/1806-9282.63.02.164 -
Journal of Cachexia, Sarcopenia and... Oct 2022One aspect of skeletal muscle memory is the ability of a previously trained muscle to hypertrophy more rapidly following a period of detraining. Although the molecular... (Meta-Analysis)
Meta-Analysis Review
One aspect of skeletal muscle memory is the ability of a previously trained muscle to hypertrophy more rapidly following a period of detraining. Although the molecular basis of muscle memory remains to be fully elucidated, one potential mechanism thought to mediate muscle memory is the permanent retention of myonuclei acquired during the initial phase of hypertrophic growth. However, myonuclear permanence is debated and would benefit from a meta-analysis to clarify the current state of the field for this important aspect of skeletal muscle plasticity. The objective of this study was to perform a meta-analysis to assess the permanence of myonuclei associated with changes in physical activity and ageing. When available, the abundance of satellite cells (SCs) was also considered given their potential influence on changes in myonuclear abundance. One hundred forty-seven peer-reviewed articles were identified for inclusion across five separate meta-analyses; (1-2) human and rodent studies assessed muscle response to hypertrophy; (3-4) human and rodent studies assessed muscle response to atrophy; and (5) human studies assessed muscle response with ageing. Skeletal muscle hypertrophy was associated with higher myonuclear content that was retained in rodents, but not humans, with atrophy (SMD = -0.60, 95% CI -1.71 to 0.51, P = 0.29, and MD = 83.46, 95% CI -649.41 to 816.32, P = 0.82; respectively). Myonuclear and SC content were both lower following atrophy in humans (MD = -11, 95% CI -0.19 to -0.03, P = 0.005, and SMD = -0.49, 95% CI -0.77 to -0.22, P = 0.0005; respectively), although the response in rodents was affected by the type of muscle under consideration and the mode of atrophy. Whereas rodent myonuclei were found to be more permanent regardless of the mode of atrophy, atrophy of ≥30% was associated with a reduction in myonuclear content (SMD = -1.02, 95% CI -1.53 to -0.51, P = 0.0001). In humans, sarcopenia was accompanied by a lower myonuclear and SC content (MD = 0.47, 95% CI 0.09 to 0.85, P = 0.02, and SMD = 0.78, 95% CI 0.37-1.19, P = 0.0002; respectively). The major finding from the present meta-analysis is that myonuclei are not permanent but are lost during periods of atrophy and with ageing. These findings do not support the concept of skeletal muscle memory based on the permanence of myonuclei and suggest other mechanisms, such as epigenetics, may have a more important role in mediating this aspect of skeletal muscle plasticity.
Topics: Animals; Atrophy; Humans; Hypertrophy; Muscle Fibers, Skeletal; Muscle, Skeletal; Sarcopenia
PubMed: 35961635
DOI: 10.1002/jcsm.13043 -
Journal of Applied Physiology... Sep 2021Satellite cells (SC) play an integral role in the recovery from skeletal muscle damage and supporting muscle hypertrophy. Acute resistance exercise typically elevates...
Satellite cells (SC) play an integral role in the recovery from skeletal muscle damage and supporting muscle hypertrophy. Acute resistance exercise typically elevates type I and type II SC content 24-96 h post exercise in healthy young males, although comparable research in females is lacking. We aimed to elucidate whether sex-based differences exist in fiber type-specific SC content after resistance exercise in the untrained (UT) and trained (T) states. Ten young males (23.0 ± 4.0 yr) and females (23.0 ± 4.8 yr) completed an acute bout of resistance exercise before and after 8 wk of whole body resistance training. Muscle biopsies were taken from the vastus lateralis immediately before and 24 and 48 h after each bout to determine SC and myonuclear content by immunohistochemistry. Males had greater SC associated with type II fibers ( ≤ 0.03). There was no effect of acute resistance exercise on SC content in either fiber type ( ≥ 0.58) for either sex; however, training increased SC in type II fibers ( < 0.01) irrespective of sex. The change in mean 0-48 h type II SC was positively correlated with muscle fiber hypertrophy in type II fibers ( = 0.47; = 0.035). Furthermore, the change in myonuclei per fiber was positively correlated with type I and type II fiber hypertrophy (both = 0.68; < 0.01). Our results suggest that SC responses to acute and chronic resistance exercise are similar in males and females and that SC and myonuclear accretion is related to training-induced muscle fiber hypertrophy. We demonstrate that training-induced increase in SC content in type II fibers and myonuclear content in type I and II fibers is similar between males and females. Furthermore, these changes are related to the extent of muscle fiber hypertrophy. Thus, SC and myonuclear accretion appear to contribute to muscle hypertrophy irrespective of sex, highlighting the importance of these muscle stem cells in human skeletal muscle growth.
Topics: Female; Humans; Hypertrophy; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Quadriceps Muscle; Resistance Training; Satellite Cells, Skeletal Muscle
PubMed: 34264129
DOI: 10.1152/japplphysiol.00424.2021 -
Journal of Applied Physiology... Dec 2020The objective was to determine whether skeletal muscle molecular markers and SC number were influenced differently in users and nonusers of oral contraceptives (OCs)...
The objective was to determine whether skeletal muscle molecular markers and SC number were influenced differently in users and nonusers of oral contraceptives (OCs) following 10 wk of resistance training. Thirty-eight young healthy untrained users ( = 20) and nonusers of OC ( = 18) completed a 10-wk supervised progressive resistance training program. Before and after the intervention, a muscle tissue sample was obtained from the vastus lateralis muscle for analysis of muscle fiber cross-sectional area (fCSA) and satellite cell (SC) and myonuclei number using immunohistochemistry, gene expression using PCR, protein expression, and myosin heavy chain composition. Following the training period, quadriceps fCSA ( < 0.05), SCs/type I fiber ( = 0.05), and MURF-1 mRNA ( < 0.01) were significantly increased with no difference between the groups. However, SCs/total fiber and SCs/type II fiber increased in OC users only, and SCs/type II fCSA tended ( = 0.055) to be greater in the OC users. Furthermore, in OC users there were a fiber type shift from myosin heavy chain (MHC) IIx to MHC IIa ( < 0.01), and expression of muscle regulatory factor 4 (MRF4) mRNA ( < 0.001) was significantly greater than in non-OC users. Use of second-generation OCs in young untrained women increased skeletal muscle MRF4 expression and SC number following 10 wk of resistance training compared with nonusers. The effect of oral contraceptive use on the skeletal muscle regulatory pathways in response to resistance training has not been investigated previously. Here we present novel data, demonstrating that use of second-generation oral contraceptives in young untrained women increased skeletal muscle regulatory factor 4 expression and satellite cell number following 10 wk of resistance training compared with nonusers.
Topics: Contraceptives, Oral; Female; Humans; Hypertrophy; Muscle Fibers, Skeletal; Muscle, Skeletal; Resistance Training
PubMed: 33054662
DOI: 10.1152/japplphysiol.00562.2020