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Medicine and Science in Sports and... Jun 2024Androgen receptor (AR) expression and signaling has been regarded as a mechanism for regulating muscle hypertrophy. However, little is known about the associations...
PURPOSE
Androgen receptor (AR) expression and signaling has been regarded as a mechanism for regulating muscle hypertrophy. However, little is known about the associations between acute and chronic changes in skeletal muscle total AR, cytoplasmic AR (cAR), nuclear AR (nAR) and AR DNA-binding (AR-DNA) induced by resistance training (RT) and hypertrophy outcomes in women and men. This study aimed to investigate the acute and chronic effects of RT on skeletal muscle total AR, cAR, nAR contents and AR-DNA in women and men. Additionally, we investigated whether these acute and chronic changes in these markers were associated with muscle hypertrophy in both sexes.
METHODS
Nineteen women and 19 men underwent 10 weeks of RT. Muscle biopsies were performed at baseline, 24 h after the first RT session and 96-120 h after the last session. AR, cAR and nAR were analyzed using Western blotting, and AR-DNA using an ELISA-oligonucleotide assay. Fiber cross-sectional area (fCSA) was analyzed through immunohistochemistry and muscle cross-sectional area (mCSA) by ultrasound.
RESULTS
At baseline, men demonstrated greater nAR than women. Baseline cAR was significantly associated with type II fCSA hypertrophy in men. Acutely, both sexes decreased AR and cAR, whereas men demonstrated greater decreases in nAR. After 10 weeks of RT, AR and nAR remained unchanged, men demonstrated greater cAR compared to women, and both sexes decreased AR-DNA activity. Acute and chronic changes in AR markers did not correlate with muscle hypertrophy (type I/II fCSA and mCSA) in women or men.
CONCLUSIONS
Baseline cAR content may influence hypertrophy in men, while neither RT-induced acute nor chronic changes in AR, cAR, nAR, and AR-DNA are associated with muscle hypertrophy in women or men.
PubMed: 38934511
DOI: 10.1249/MSS.0000000000003509 -
Journal of Applied Physiology... Jun 2024Resistance training (RT) remains the most effective treatment for age-related declines in muscle mass. However, many older adults experience attenuated muscle...
Resistance training (RT) remains the most effective treatment for age-related declines in muscle mass. However, many older adults experience attenuated muscle hypertrophy in response to RT when compared to younger adults. This may be attributed to underlying molecular processes that are dysregulated by aging and exacerbated by improperly prescribed RT weekly volume, intensity, and/or frequency doses. MicroRNA (miRNA) are key epigenetic regulators that impact signaling pathways and protein expression within cells, are dynamic and responsive to exercise stimuli, and are often dysregulated in diseases. In this study, we used untargeted miRNA-seq to examine miRNA in skeletal muscle and serum-derived exosomes of older adults (n = 18, 11M/7F, 66±1y) who underwent 3x/wk RT for 30 weeks [e.g., high intensity 3x/wk (HHH, n = 9) or alternating high-low-high intensity (HLH, n = 9)], after a standardized four-week wash-in. Within each tissue, miRNAs were clustered into modules based on pairwise correlation using Weighted Gene Correlation Network Analysis (WGCNA). Modules were tested for association with the magnitude of RT-induced thigh lean mass (TLM) change (as measured by DXA). While no modules were unique to training dose, we identified miRNA modules in skeletal muscle associated with TLM gains irrespective of exercise dose. Using miRNA-target interactions, we analyzed key miRNAs in significant modules for their potential regulatory involvement in biological pathways. Findings point toward potential miRNAs that may be informative biomarkers and could also be evaluated as potential therapeutic targets as an adjuvant to RT in order to maximize skeletal muscle mass accrual in older adults.
PubMed: 38932684
DOI: 10.1152/japplphysiol.00680.2023 -
Nutrients Jun 2024It is a common belief amongst strength and power athletes that nutritional supplementation strategies aid recovery by shifting the anabolic/catabolic profile toward... (Review)
Review
It is a common belief amongst strength and power athletes that nutritional supplementation strategies aid recovery by shifting the anabolic/catabolic profile toward anabolism. Factors such as nutrient quantity, nutrient quality, and nutrient timing significantly impact upon the effectiveness of nutritional strategies in optimizing the acute responses to resistance exercise and the adaptive response to resistance training (i.e., muscle growth and strength expression). Specifically, the aim of this review is to address carbohydrates (CHOs), protein (PRO), and/or amino acids (AAs) supplementation strategies, as there is growing evidence suggesting a link between nutrient signaling and the initiation of protein synthesis, muscle glycogen resynthesis, and the attenuation of myofibrillar protein degradation following resistance exercise. Collectively, the current scientific literature indicates that nutritional supplementation strategies utilizing CHO, PRO, and/or AA represents an important approach aimed at enhancing muscular responses for strength and power athletes, primarily increased muscular hypertrophy and enhanced strength expression. There appears to be a critical interaction between resistance exercise and nutrient-cell signaling associated with the principle of nutrient timing (i.e., pre-exercise, during, and post-exercise). Recommendations for nutritional supplementation strategies to promote muscular responses for strength and athletes are provided.
Topics: Humans; Dietary Supplements; Dietary Proteins; Dietary Carbohydrates; Resistance Training; Amino Acids; Athletes; Muscle, Skeletal; Muscle Strength; Sports Nutritional Physiological Phenomena
PubMed: 38931241
DOI: 10.3390/nu16121886 -
Cell Death & Disease Jun 2024Pathological cardiac hypertrophy is one of the major risk factors of heart failure and other cardiovascular diseases. However, the mechanisms underlying pathological...
Pathological cardiac hypertrophy is one of the major risk factors of heart failure and other cardiovascular diseases. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. Here, we identified the first evidence that TNFAIP3 interacting protein 3 (TNIP3) was a negative regulator of pathological cardiac hypertrophy. We observed a significant upregulation of TNIP3 in mouse hearts subjected to transverse aortic constriction (TAC) surgery and in primary neonatal rat cardiomyocytes stimulated by phenylephrine (PE). In Tnip3-deficient mice, cardiac hypertrophy was aggravated after TAC surgery. Conversely, cardiac-specific Tnip3 transgenic (TG) mice showed a notable reversal of the same phenotype. Accordingly, TNIP3 alleviated PE-induced cardiomyocyte enlargement in vitro. Mechanistically, RNA-sequencing and interactome analysis were combined to identify the signal transducer and activator of transcription 1 (STAT1) as a potential target to clarify the molecular mechanism of TNIP3 in pathological cardiac hypertrophy. Via immunoprecipitation and Glutathione S-transferase assay, we found that TNIP3 could interact with STAT1 directly and suppress its degradation by suppressing K48-type ubiquitination in response to hypertrophic stimulation. Remarkably, preservation effect of TNIP3 on cardiac hypertrophy was blocked by STAT1 inhibitor Fludaradbine or STAT1 knockdown. Our study found that TNIP3 serves as a novel suppressor of pathological cardiac hypertrophy by promoting STAT1 stability, which suggests that TNIP3 could be a promising therapeutic target of pathological cardiac hypertrophy and heart failure.
Topics: Animals; Cardiomegaly; STAT1 Transcription Factor; Myocytes, Cardiac; Mice; Rats; Male; Mice, Inbred C57BL; Ubiquitination; Membrane Proteins; Mice, Transgenic; Humans; Phenylephrine; Protein Stability; Mice, Knockout
PubMed: 38926347
DOI: 10.1038/s41419-024-06805-4 -
Physiological Reports Jun 2024Cardiac hypertrophy is an adaptive response to stressors such as high cardiac workload, which might lead to abnormal cardiac function and heart failure. Previous studies...
Cardiac hypertrophy is an adaptive response to stressors such as high cardiac workload, which might lead to abnormal cardiac function and heart failure. Previous studies have indicated that macrophage migration inhibitory factor (MIF) might play a protective role in cardiac hypertrophy. Here, we aimed to illustrate the mechanism of MIF in protecting against pressure overload-induced cardiac hypertrophy. Transverse aortic constriction (TAC) mouse model was established and we found that overexpression of MIF protected against pressure overload-induced cardiac hypotrophy in TAC treated mice, as evidenced by significantly decreased the heart weight. In addition, transthoracic echocardiography showed that overexpression of MIF restored ejection fraction in TAC-treated mice. While TAC treatment resulted in a much larger cardiomyocyte size in mice, MIF overexpression notably decreased the cardiomyocyte size. Next, we demonstrated that MIF overexpression promoted the expression of miR-29b-3p which further downregulated the expression of its downstream target HMG box protein 1 (HBP1). Overexpression of HBP1 reversed the effect of MIF in alleviating Ang-II induced oxidative stress in cardiomyocytes. In conclusion, our findings suggest that MIF could attenuate pressure overload-induced cardiac hypertrophy through regulating the miR-29b-3p/HBP1 axis.
Topics: Animals; Macrophage Migration-Inhibitory Factors; MicroRNAs; Cardiomegaly; Mice; Male; Myocytes, Cardiac; Mice, Inbred C57BL; HMGB1 Protein; Oxidative Stress; Intramolecular Oxidoreductases
PubMed: 38924383
DOI: 10.14814/phy2.16022 -
Pflugers Archiv : European Journal of... Jun 2024This study investigated the effect of a resistance training (R) period at terrestrial (HH) and normobaric hypoxia (NH) on both muscle hypertrophy and maximal strength...
This study investigated the effect of a resistance training (R) period at terrestrial (HH) and normobaric hypoxia (NH) on both muscle hypertrophy and maximal strength development with respect to the same training in normoxia (N). Thirty-three strength-trained males were assigned to N (FiO = 20.9%), HH (2,320 m asl) or NH (FiO = 15.9%). The participants completed an 8-week R program (3 sessions/week) of a full body routine. Muscle thickness of the lower limb and 1RM in back squat were assessed before and after the training program. Blood markers of stress, inflammation (IL-6) and muscle growth (% active mTOR, myostatin and miRNA-206) were measured before and after the first and last session of the program. Findings revealed all groups improved 1RM, though this was most enhanced by R in NH (p = 0.026). According to the moderate to large excess of the exercise-induced stress response (lactate and Ca) in HH and N, results only displayed increases in muscle thickness in these two conditions over NH (ES > 1.22). Compared with the rest of the environmental conditions, small to large increments in % active mTOR were only found in HH, and IL-6, myostatin and miR-206 in NH throughout the training period. In conclusion, the results do not support the expected additional benefit of R under hypoxia compared to N on muscle growth, although it seems to favour gains in strength. The greater muscle growth achieved in HH over NH confirms the impact of the type of hypoxia on the outcomes.
PubMed: 38916665
DOI: 10.1007/s00424-024-02978-1 -
Clinical Case Reports Jul 2024Botulinum toxin (BTX) injection can be an effective treatment for persistent pain and functional impairment associated with hypertrophy of the first dorsal interosseous...
Botulinum toxin (BTX) injection can be an effective treatment for persistent pain and functional impairment associated with hypertrophy of the first dorsal interosseous muscle. It offers a non-surgical and minimally invasive alternative for those who have failed conservative treatment, showcasing the therapeutic promise of BTX for addressing similar musculoskeletal conditions.
PubMed: 38915929
DOI: 10.1002/ccr3.9094 -
Scientific Reports Jun 2024The present study aimed to assess the effectiveness and functional adverse effects of a single and multiple injections of botulinum toxin A (BoNT-A) for masseter... (Randomized Controlled Trial)
Randomized Controlled Trial
The present study aimed to assess the effectiveness and functional adverse effects of a single and multiple injections of botulinum toxin A (BoNT-A) for masseter hypertrophy (MH). Twenty-six women complaining about lower third facial enlargement due to MH, received 75 U of BoNT-A (abobotulinum toxin) in each masseter muscles. After 3 months, patients were randomly assigned to receive a second treatment session of Saline Solution: (G1; n = 11) or BoNT-A: (G2; n = 12). Muscle thickness (ultrasound), electrical activity (electromyography; EMG), masticatory performance, and subjective perception of MH were evaluated. Follow-up was performed at 1, 3 and 6 months. Muscle thickness, EMG activity, and masticatory performance were analyzed using ANOVA two-way and Sidak test as post-hoc. Masticatory performance was analyzed by the Friedman's test and Mann-Whitney test. Regarding inter-groups comparisons, there was a significant decrease in the left masseter muscle thickness in the G2 group at the 6 month follow-up (p < 0.02). For EMG, significant differences were evident at the 6 month assessment, with higher masseter activity for G1 (p < 0.05). For masticatory performance, no significant differences were observed throughout the study (p > 0.05) and a higher improvement in subjective perception of MH was observed in the 1 month follow-up for G2 (p < 0.05). In conclusion, BoNT-A is effective for MH, however multiple injections cause functional adverse effects in masseter muscle.
Topics: Humans; Masseter Muscle; Female; Hypertrophy; Botulinum Toxins, Type A; Adult; Electromyography; Mastication; Middle Aged; Treatment Outcome; Neuromuscular Agents; Injections, Intramuscular
PubMed: 38914688
DOI: 10.1038/s41598-024-65395-5 -
PloS One 2024The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This...
The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis.
Topics: Animals; Asthma; Rosuvastatin Calcium; AMP-Activated Protein Kinases; Signal Transduction; Airway Remodeling; Mice; Disease Models, Animal; Ovalbumin; Female; Mice, Inbred BALB C; Bronchoalveolar Lavage Fluid; Chronic Disease; Inflammation; Lung; Immunoglobulin E
PubMed: 38913666
DOI: 10.1371/journal.pone.0305863 -
American Journal of Physiology. Cell... Jun 2024In cell biology, ribosomal RNA (rRNA) 2'-methyl (2'--Me) is the most prevalent post-transcriptional chemical modification contributing to ribosome heterogeneity. The...
In cell biology, ribosomal RNA (rRNA) 2'-methyl (2'--Me) is the most prevalent post-transcriptional chemical modification contributing to ribosome heterogeneity. The modification involves a family of small nucleolar RNAs (snoRNAs) and is specified by box C/D snoRNAs (SNORDs). Given the importance of ribosome biogenesis for skeletal muscle growth, we asked if rRNA 2'--Me in nascent ribosomes synthesized in response to a growth stimulus is an unrecognized mode of ribosome heterogeneity in muscle. To determine the pattern and dynamics of 2'--Me rRNA, we used a sequencing-based profiling method called RiboMeth-seq. We applied this method to tissue-derived rRNA of skeletal muscle and rRNA specifically from the muscle fiber using an inducible myofiber-specific RiboTag mouse in sedentary and mechanically overloaded conditions. These analyses were complemented by myonuclear-specific small RNA sequencing to profile SNORDs and link the rRNA epitranscriptome to known regulatory elements generated within the muscle fiber. We demonstrate for the first time that mechanical overload of skeletal muscle 1) induces 2'--Me at a subset of skeletal muscle rRNAand 2) alters the SNORD profile in isolated myonuclei. These findings point to a transient diversification of the ribosome pool via 2'--Me during growth and adaptation in skeletal muscle. These findings suggest changes in ribosome heterogeneity at the 2'--Me level during muscle hypertrophy and lay the foundation for studies investigating the functional implications of these newly identified "growth-induced" ribosomes.
PubMed: 38912733
DOI: 10.1152/ajpcell.00301.2024