Although transcriptome profiling has been used in several resistance training studies, the associated analytical approaches seldom provide in-depth information on individual genes linked to skeletal muscle hypertrophy. Therefore, a secondary analysis was performed herein on a muscle transcriptomic dataset we previously published involving trained college-aged men (n = 11) performing two resistance exercise bouts in a randomized and crossover fashion. The lower-load bout (30 Fail) consisted of 8 sets of lower body exercises to volitional fatigue using 30% one-repetition maximum (1 RM) loads, whereas the higher-load bout (80 Fail) consisted of the same exercises using 80% 1 RM loads. Vastus lateralis muscle biopsies were collected prior to (PRE), 3 h, and 6 h after each exercise bout, and 58 genes associated with skeletal muscle hypertrophy were manually interrogated from our prior microarray data. Select targets were further interrogated for associated protein expression and phosphorylation induced-signaling events. Although none of the 58 gene targets demonstrated significant bout x time interactions, ~57% (32 genes) showed a significant main effect of time from PRE to 3 h (15↑ and 17↓, p < 0.01), and ~26% (17 genes) showed a significant main effect of time from PRE to 6 h (8↑ and 9↓, p < 0.01). Notably, genes associated with the myostatin (9 genes) and mammalian target of rapamycin complex 1 (mTORC1) (9 genes) signaling pathways were most represented. Compared to mTORC1 signaling mRNAs, more MSTN signaling-related mRNAs (7 of 9) were altered post-exercise, regardless of the bout, and RHEB was the only mTORC1-associated mRNA that was upregulated following exercise. Phosphorylated (phospho-) p70S6K (Thr389) (p = 0.001; PRE to 3 h) and follistatin protein levels (p = 0.021; PRE to 6 h) increased post-exercise, regardless of the bout, whereas phospho-AKT (Thr389), phospho-mTOR (Ser2448), and myostatin protein levels remained unaltered. These data continue to suggest that performing resistance exercise to volitional fatigue, regardless of load selection, elicits similar transient mRNA and signaling responses in skeletal muscle. Moreover, these data provide further evidence that the transcriptional regulation of myostatin signaling is an involved mechanism in response to resistance exercise.

Background: While canonical anabolic and proteolytic pathways have been well examined in the context of skeletal muscle proteostasis, the roles of endoplasmic reticulum stress (ERS) and the induced unfolded protein response (UPR) are underappreciated. Thus, we aimed to determine whether aging and/or disuse atrophy in rats altered skeletal muscle ERS/UPR markers. Methods and Results: Soleus (SOL) and plantaris (PLT) muscles of 3-month-old (mo), 6 mo, 12 mo, 18 mo, and 24 mo rats (9–10 per group, 48 in total) were analyzed for UPR proteins with further analysis performed on the protein CHOP. The gastrocnemius muscles of 4 mo rats that had undergone hindlimb immobilization (HLI, n = 12) or sham casting (CTL, n = 12) were analyzed for similar targets as well as more extensive CHOP-related targets. CHOP protein was greater in the PLT and SOL of 18 and 24 mo rats versus other age groups ( P < 0.05). Moreover, negative correlations existed between CHOP expression and normalized PLT ( R =-0.702, P < 0.001) and SOL ( R =-0.658, P < 0.001) muscle weights in all rats analyzed at different ages. CHOP protein expression was also greater in the gastrocnemius of HLI versus CTL rats ( P < 0.001), and a negative correlation existed between CHOP protein expression and normalized muscle weights in these rats ( R =-0.814, P < 0.001). Nuclear CHOP protein levels ( P < 0.010) and genes transcriptionally regulated by CHOP were also greater in HLI versus CTL rats ( P < 0.001) implicating transcriptional activity of CHOP is elevated during disuse atrophy. Conclusions: CHOP is operative during aging- and disuse-induced skeletal muscle atrophy in rodents, and more research is needed to determine if CHOP is a key mechanistic driver of these processes.

We examined how set-volume equated resistance training using either the back squat (SQ) or hip thrust (HT) affected hypertrophy and various strength outcomes. Untrained college-aged participants were randomized into HT (n = 18) or SQ (n = 16) groups. Surface electromyograms (sEMG) from the right gluteus maximus and medius muscles were obtained during the first training session. Participants completed 9 weeks of supervised training (15–17 sessions), before and after which gluteus and leg muscle cross-sectional area (mCSA) was assessed via magnetic resonance imaging. Strength was also assessed prior to and after the training intervention via three-repetition maximum (3RM) testing and an isometric wall push test. Gluteus mCSA increases were similar across both groups. Specifically, estimates [(−) favors HT (+) favors SQ] modestly favored the HT versus SQ for lower [effect ±SE, −1.6 ± 2.1 cm²; CI_95% (−6.1, 2.0)], mid [−0.5 ± 1.7 cm²; CI_95% (−4.0, 2.6)], and upper [−0.5 ± 2.6 cm²; CI_95% (−5.8, 4.1)] gluteal mCSAs but with appreciable variance. Gluteus medius + minimus [−1.8 ± 1.5 cm²; CI_95% (−4.6, 1.4)] and hamstrings [0.1 ± 0.6 cm²; CI_95% (−0.9, 1.4)] mCSA demonstrated little to no growth with small differences between groups. mCSA changes were greater in SQ for the quadriceps [3.6 ± 1.5 cm²; CI_95% (0.7, 6.4)] and adductors [2.5 ± 0.7 cm²; CI_95% (1.2, 3.9)]. Squat 3RM increases favored SQ [14 ± 2 kg; CI_95% (9, 18),] and hip thrust 3RM favored HT [−26 ± 5 kg; CI_95% (−34, −16)]. 3RM deadlift [0 ± 2 kg; CI_95% (−4, 3)] and wall push strength [−7 ± 12N; CI_95% (−32, 17)] similarly improved. All measured gluteal sites showed greater mean sEMG amplitudes during the first bout hip thrust versus squat set, but this did not consistently predict gluteal hypertrophy outcomes. Squat and hip thrust training elicited similar gluteal hypertrophy, greater thigh hypertrophy in SQ, strength increases that favored exercise allocation, and similar deadlift and wall push strength increases.

We examined how resistance exercise (RE), cycling exercise and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation. The 1boutRE study involved younger men ( n = 8; 5 ± 2 years of RE experience) performing a lower body RE bout with vastus lateralis (VL) biopsies being obtained prior to and acutely following exercise. With the 10weekRT study, VL biopsies were obtained in 36 younger adults before and 24 h after their first/naïve RE bout. Participants also engaged in 10 weeks of resistance training and donated VL biopsies before and 24 h after their last RE bout. VL biopsies were also examined in an acute cycling study ( n = 7) and a study involving 2 weeks of leg immobilization ( n = 20). In the 1boutRE study, fragmentation of all MyHC isoforms (MyHC _Total ) increased 3 h post‐RE (∼200%, P = 0.018) and returned to pre‐exercise levels by 6 h post‐RE. Interestingly, a greater magnitude increase in MyHC type IIa versus I isoform fragmentation occurred 3 h post‐RE (8.6 ± 6.3‐fold vs. 2.1 ± 0.7‐fold, P = 0.018). In 10weekRT participants, the first/naïve and last RE bouts increased MyHC _Total fragmentation 24 h post‐RE (+65% and +36%, P  < 0.001); however, the last RE bout response was attenuated compared to the first bout ( P = 0.045). Although cycling exercise did not alter MyHC _Total fragmentation, ∼8% VL atrophy with 2 weeks of leg immobilization increased MyHC _Total fragmentation (∼108%, P  < 0.001). Mechanistic C ₂ C ₁₂ myotube experiments indicated that MyHC _Total fragmentation is likely due to calpain proteases. In summary, RE and disuse atrophy increase MyHC protein fragmentation. Research into how ageing and disease‐associated muscle atrophy affect these outcomes is needed. Highlights: What is the central question of this study? How different exercise stressors and disuse affect skeletal muscle myosin heavy chain fragmentation. What is the main finding and its importance? This investigation is the first to demonstrate that resistance exercise and disuse atrophy lead to skeletal muscle myosin heavy chain protein fragmentation in humans. Mechanistic in vitro experiments provide additional evidence that MyHC fragmentation occurs through calpain proteases.

As a follow-up to our original investigation by Michel JM et al. J Appl Physiol (1985) 138: 450–467, 2025, we sought to examine how limb immobilization and recovery resistance training affect molecular outcomes related to angiogenesis in younger adults with or without a prior training history. Regardless of resistance training history, the molecular responses are largely similar between participant cohorts and are suggestive of a reduced (PRE-MID) and increased (MID-POST) angiogenic response, with disuse and subsequent recovery resistance training.

Results from this study suggest that 12 wk of dietary nitrate supplementation does not significantly alter skeletal muscle hypertrophic, strength, or vascular outcomes in previously untrained middle-aged and older adults who performed resistance training.