An intron variant of the GLI family zinc finger 3 (GLI3) gene differentiates resistance training-induced muscle fiber hypertrophy in younger men.

We examined the association between genotype and resistance training-induced changes (12 wk) in dual x-ray energy absorptiometry (DXA)-derived lean soft tissue mass (LSTM) as well as muscle fiber cross-sectional area (fCSA; vastus lateralis; n = 109; age = 22 ± 2 y, BMI = 24.7 ± 3.1 kg/m2 ). Over 315 000 genetic polymorphisms were interrogated from muscle using DNA microarrays. First, a targeted investigation was performed where single nucleotide polymorphisms (SNP) identified from a systematic literature review were related to changes in LSTM and fCSA. Next, genome-wide association (GWA) studies were performed to reveal associations between novel SNP targets with pre- to post-training change scores in mean fCSA and LSTM. Our targeted investigation revealed no genotype-by-time interactions for 12 common polymorphisms regarding the change in mean fCSA or change in LSTM. Our first GWA study indicated no SNP were associated with the change in LSTM. However, the second GWA study indicated two SNP exceeded the significance level with the change in mean fCSA (P = 6.9 × 10-7 for rs4675569, 1.7 × 10-6 for rs10263647). While the former target is not annotated (chr2:205936846 (GRCh38.p12)), the latter target (chr7:41971865 (GRCh38.p12)) is an intron variant of the GLI Family Zinc Finger 3 (GLI3) gene. Follow-up analyses indicated fCSA increases were greater in the T/C and C/C GLI3 genotypes than the T/T GLI3 genotype (P < .05). Data from the Auburn cohort also revealed participants with the T/C and C/C genotypes exhibited increases in satellite cell number with training (P < .05), whereas T/T participants did not. Additionally, those with the T/C and C/C genotypes achieved myonuclear addition in response to training (P < .05), whereas the T/T participants did not. In summary, this is the first GWA study to examine how polymorphisms associate with the change in hypertrophy measures following resistance training. Future studies are needed to determine if the GLI3 variant differentiates hypertrophic responses to resistance training given the potential link between this gene and satellite cell physiology.

Both Traditional and Stair Climbing-based HIIT Cardiac Rehabilitation Induce Beneficial Muscle Adaptations.

PURPOSE: There is a lack of knowledge as to how different exercise-based cardiac rehabilitation programming affects skeletal muscle adaptations in coronary artery disease (CAD) patients. We first characterized the skeletal muscle from adults with CAD compared with a group of age- and sex-matched healthy adults. We then determined the effects of a traditional moderate-intensity continuous exercise program (TRAD) or a stair climbing-based high-intensity interval training program (STAIR) on skeletal muscle metabolism in CAD. METHODS: Sixteen adults (n = 16, 61 ± 7 yr), who had undergone recent treatment for CAD, were randomized to perform (3 d·wk-1) either TRAD (n = 7, 30 min at 60%-80% of peak heart rate) or STAIR (n = 9, 3 × 6 flights) for 12 wk. Muscle biopsies were collected at baseline in both CAD and healthy controls (n = 9), and at 4 and 12 wk after exercise training in CAD patients undertaking TRAD or STAIR. RESULTS: We found that CAD had a lower capillary-to-fiber ratio (C/Fi, 35% ± 25%, P = 0.06) and capillary-to-fiber perimeter exchange (CFPE) index (23% ± 29%, P = 0.034) in Type II fibers compared with healthy controls. However, 12 wk of cardiac rehabilitation with either TRAD or STAIR increased C/Fi (Type II, 23% ± 14%, P < 0.001) and CFPE (Type I, 10% ± 23%, P < 0.01; Type II, 18% ± 22%, P = 0.002). CONCLUSION: Cardiac rehabilitation via TRAD or STAIR exercise training improved the compromised skeletal muscle microvascular phenotype observed in CAD patients.

Presleep α-Lactalbumin Consumption Does Not Improve Sleep Quality or Time-Trial Performance in Cyclists.

We tested the hypothesis that presleep consumption of α-lactalbumin (LA), a fraction of whey with a high abundance of tryptophan, would improve indices of sleep quality and time-trial (TT) performance in cyclists relative to an isonitrogenous collagen peptide (CP) supplement lacking tryptophan. Using randomized, double-blind, crossover designs, cyclists consumed either 40 g of LA or CP 2 hr prior to sleep. In Study 1, six elite male endurance track cyclists (age 23 ± 6 years, V˙O2peak 70.2 ± 4.4 ml·kg-1·min-1) consumed a supplement for three consecutive evenings before each 4-km TT on a velodrome track, whereas in Study 2, six well-trained cyclists (one female; age 24 ± 5 years, V˙O2peak 66.9 ± 8.3 ml·kg-1·min-1) consumed a supplement the evening before each 4-km TT on a stationary cycle ergometer. Indices of sleep quality were assessed with wrist-based actigraphy. There were no differences between the CP and LA supplements in terms of total time in bed, total sleep time, or sleep efficiency in Study 1 (LA: 568 ± 71 min, 503 ± 67 min, 88.3% ± 3.4%; CP: 546 ± 30 min, 479 ± 35 min, 87.8% ± 3.1%; p = .41, p = .32, p = .74, respectively) or Study 2 (LA: 519 ± 90 min, 450 ± 78 min, 87.2% ± 7.6%; CP: 536 ± 62 min, 467 ± 57 min, 87.3% ± 6.4%; p = .43, p = .44, p = .97, respectively). Similarly, time to complete the 4-km TT was unaffected by supplementation in Study 1 (LA: 274.9 ± 7.6 s; CP: 275.5 ± 7.2 s; p = .62) and Study 2 (LA: 344.3 ± 22.3 s; CP: 343.3 ± 23.0 s; p = .50). Thus, relative to CP, consuming LA 2 hr prior to sleep over 1-3 days did not improve actigraphy-based indices of sleep quality or 4-km TT performance in cyclists.

Whey protein but not collagen peptides stimulate acute and longer-term muscle protein synthesis with and without resistance exercise in healthy older women: a randomized controlled trial.

BACKGROUND: Aging appears to attenuate the response of skeletal muscle protein synthesis (MPS) to anabolic stimuli such as protein ingestion (and the ensuing hyperaminoacidemia) and resistance exercise (RE). OBJECTIVES: The purpose of this study was to determine the effects of protein quality on feeding- and feeding plus RE-induced increases of acute and longer-term MPS after ingestion of whey protein (WP) and collagen protein (CP). METHODS: In a double-blind parallel-group design, 22 healthy older women (mean ± SD age: 69 ± 3 y, n = 11/group) were randomly assigned to consume a 30-g supplement of either WP or CP twice daily for 6 d. Participants performed unilateral RE twice during the 6-d period to determine the acute (via [13C6]-phenylalanine infusion) and longer-term (ingestion of deuterated water) MPS responses, the primary outcome measures. RESULTS: Acutely, WP increased MPS by a mean ± SD 0.017 ± 0.008%/h in the feeding-only leg (Rest) and 0.032 ± 0.012%/h in the feeding plus exercise leg (Exercise) (both P < 0.01), whereas CP increased MPS only in Exercise (0.012 ± 0.013%/h) (P < 0.01) and MPS was greater in WP than CP in both the Rest and Exercise legs (P = 0.02). Longer-term MPS increased by 0.063 ± 0.059%/d in Rest and 0.173 ± 0.104%/d in Exercise (P < 0.0001) with WP; however, MPS was not significantly elevated above baseline in Rest (0.011 ± 0.042%/d) or Exercise (0.020 ± 0.034%/d) with CP. Longer-term MPS was greater in WP than in CP in both Rest and Exercise (P < 0.001). CONCLUSIONS: Supplementation with WP elicited greater increases in both acute and longer-term MPS than CP supplementation, which is suggestive that WP is a more effective supplement to support skeletal muscle retention in older women than CP.This trial was registered at clinicaltrials.gov as NCT03281434.

The Impact of Step Reduction on Muscle Health in Aging: Protein and Exercise as Countermeasures.

Declines in strength and muscle function with age-sarcopenia-contribute to a variety of negative outcomes including an increased risk of: falls, fractures, hospitalization, and reduced mobility in older persons. Population-based estimates of the loss of muscle after age 60 show a loss of ~1% per year while strength loss is more rapid at ~3% per year. These rates are not, however, linear as periodic bouts of reduced physical activity and muscle disuse transiently accelerate loss of muscle and declines in muscle strength and power. Episodic complete muscle disuse can be due to sickness-related bed rest or local muscle disuse as a result of limb immobilization/surgery. Alternatively, relative muscle disuse occurs during inactivity due to illness and the associated convalescence resulting in marked reductions in daily steps, often referred to as step reduction (SR). While it is a "milder" form of disuse, it can have a similar adverse impact on skeletal muscle health. The physiological consequences of even short-term inactivity, modeled by SR, show losses in muscle mass and strength, as well as impaired insulin sensitivity and an increase in systemic inflammation. Though seemingly benign in comparison to bed rest, periodic inactivity likely occurs, we posit, more frequently with advancing age due to illness, declining mental health and declining mobility. Given that recovery from inactivity in older adults is slow or possibly incomplete we hypothesize that accumulated periods of inactivity contribute to sarcopenia. Periodic activity, even in small quantities, and protein supplementation may serve as effective strategies to offset the loss of muscle mass with aging, specifically during periods of inactivity. The aim of this review is to examine the recent literature encompassing SR, as a model of inactivity, and to explore the capacity of nutrition and exercise interventions to mitigate adverse physiological changes as a result of SR.

Maintenance of skeletal muscle function following reduced daily physical activity in healthy older adults: a pilot trial.

Older adults can experience periods of inactivity related to disease or illness, which can hasten the development of physical disability, in part, through reductions in skeletal muscle strength and power. To date no study has characterized adaptations in skeletal muscle physical function in response to reduced daily physical activity. Participants (15 men, aged 69 ± 2 years; 15 women, aged 68 ± 4 years) restricted their daily steps (<750 steps/day) while being energy restricted (-500 kcal/day) for 2 weeks before returning to normal activity levels during recovery (RC; 1 week). Before and after each phase, measures of knee extensor isometric maximum voluntary contraction (MVC), time-to-peak torque, and physical function were performed and muscle biopsies were taken from a subset of participants. Following the energy restriction and step-reduction phase (ER+SR), MVC was reduced by 9.1 and 6.1 Nm in men and women, respectively (p = 0.02), which returned to baseline after RC in men, but not women (p = 0.046). Maximum isometric tension in MHC IIA fibres (p < 0.01) and maximum power production in MHC I and IIA (p = 0.05) were increased by 14%, 25%, and 10%, respectively, following ER+SR. Reductions in muscle strength could not be explained by changes in single muscle fibre function in a subsample (n = 9 men) of volunteers. These data highlight the resilience of physical function in healthy older men in the face of an acute period of ER+SR and demonstrate sex-based differences in the ability to recover muscle strength upon resumption of physical activity.

A randomized controlled trial of the impact of protein supplementation on leg lean mass and integrated muscle protein synthesis during inactivity and energy restriction in older persons.

Background: In older persons, muscle loss is accelerated during physical inactivity and hypoenergetic states, both of which are features of hospitalization. Protein supplementation may represent a strategy to offset the loss of muscle during inactivity, and enhance recovery on resumption of activity. Objective: We aimed to determine if protein supplementation, with proteins of substantially different quality, would alleviate the loss of lean mass by augmenting muscle protein synthesis (MPS) while inactive during a hypoenergetic state. Design: Participants (16 men, mean ± SD age: 69 ± 3 y; 15 women, mean ± SD age: 68 ± 4 y) consumed a diet containing 1.6 g protein · kg-1 · d-1, with 55% ± 9% of protein from foods and 45% ± 9% from supplements, namely, whey protein (WP) or collagen peptides (CP): 30 g each, consumed 2 times/d. Participants were in energy balance (EB) for 1 wk, then began a period of energy restriction (ER; -500 kcal/d) for 1 wk, followed by ER with step reduction (ER + SR; <750 steps/d) for 2 wk, before a return to habitual activity in recovery (RC) for 1 wk. Results: There were significant reductions in leg lean mass (LLM) from EB to ER, and from ER to ER + SR in both groups (P < 0.001) with no differences between WP and CP or when comparing the change from phase to phase. During RC, LLM increased from ER + SR, but in the WP group only. Rates of integrated muscle protein synthesis decreased during ER and ER + SR in both groups (P < 0.01), but increased during RC only in the WP group (P = 0.05). Conclusions: Protein supplementation did not confer a benefit in protecting LLM, but only supplemental WP augmented LLM and muscle protein synthesis during recovery from inactivity and a hypoenergetic state. This trial was registered at http://www.clinicaltrials.gov as NCT03285737.

Microvascular adaptations to resistance training are independent of load in resistance-trained young men.

Resistance training promotes microvasculature expansion; however, it remains unknown how different resistance training programs contribute to angiogenesis. Thus, we recruited experienced resistance-trained participants and determined the effect of 12 wk of either high-repetition/low-load or low-repetition/high-load resistance training performed to volitional fatigue on muscle microvasculature. Twenty men performed either a high-repetition [20-25 repetitions, 30-50% of 1-repetition maximum (1RM); n = 10] or a low-repetition (8-12 repetitions, 75-90% of 1RM; n = 10) resistance training program. Muscle biopsies were taken before and after resistance training, and immunohistochemistry was used to assess fiber type (I and II)-specific microvascular variables. High-repetition/low-load and low-repetition/high-load groups were not different in any variable before resistance training. Both protocols resulted in an increase in capillarization. Specifically, after resistance training, the capillary-to-fiber ratio, capillary contacts, and capillary-to-fiber perimeter exchange index were elevated, and sharing factor was reduced. These data demonstrate that resistance training performed to volitional failure, using either high repetition/low load or low repetition/high load, induced similar microvascular adaptations in recreationally resistance-trained young men.

Assessing the mechanistic target of rapamycin complex-1 pathway in response to resistance exercise and feeding in human skeletal muscle by multiplex assay.

The mechanistic target of rapamycin complex-1 (mTORC-1) is a key nutrient and contraction-sensitive protein that regulates a pathway leading to skeletal muscle growth. Utilizing a multiplex assay, we aimed to examine the phosphorylation status of key mTORC-1-related signalling molecules in response to protein feeding and resistance exercise. Eight healthy men (age, 22.5 ± 3.1 years; mass, 80 ± 9 kg; 1-repetition maximum leg extension, 87 ± 5 kg) performed 4 sets of unilateral leg extensions until volitional failure. Immediately following the final set, all participants consumed a protein-enriched beverage. A single skeletal muscle biopsy was obtained from the vastus lateralis before (Pre) with further bilateral biopsies at 1 h (1 h exercised legs (FEDEX) and 1 h nonexercised legs (FED)) and 3 h (3 h FEDEX and 3 h FED) after drink ingestion. Phosphorylated AktSer473 was significantly elevated from Pre at 1 h FEDEX. Phosphorylated p70S6K1Thr412 was significantly increased above Pre at 1 h FEDEX and 1 h FED and was still significantly elevated at 3 h FEDEX but not 3 h FED. Phosphorylated rpS6Ser235/236 was also significantly increased above Pre at 1 h FEDEX and 1 h FED with 1 h FEDEX greater than 1 h FED. Our data highlight the utility of a multiplex assay to assess anabolic signalling molecules in response to protein feeding and resistance exercise in humans. Importantly, these changes are comparable with those as previously reported using standard immunoblotting and protein activity assays.

Differential localization and anabolic responsiveness of mTOR complexes in human skeletal muscle in response to feeding and exercise.

Mechanistic target of rapamycin (mTOR) resides as two complexes within skeletal muscle. mTOR complex 1 [mTORC1-regulatory associated protein of mTOR (Raptor) positive] regulates skeletal muscle growth, whereas mTORC2 [rapamycin-insensitive companion of mTOR (Rictor) positive] regulates insulin sensitivity. To examine the regulation of these complexes in human skeletal muscle, we utilized immunohistochemical analysis to study the localization of mTOR complexes before and following protein-carbohydrate feeding (FED) and resistance exercise plus protein-carbohydrate feeding (EXFED) in a unilateral exercise model. In basal samples, mTOR and the lysosomal marker lysosomal associated membrane protein 2 (LAMP2) were highly colocalized and remained so throughout. In the FED and EXFED states, mTOR/LAMP2 complexes were redistributed to the cell periphery [wheat germ agglutinin (WGA)-positive staining] (time effect; P = 0.025), with 39% (FED) and 26% (EXFED) increases in mTOR/WGA association observed 1 h post-feeding/exercise. mTOR/WGA colocalization continued to increase in EXFED at 3 h (48% above baseline) whereas colocalization decreased in FED (21% above baseline). A significant effect of condition (P = 0.05) was noted suggesting mTOR/WGA colocalization was greater during EXFED. This pattern was replicated in Raptor/WGA association, where a significant difference between EXFED and FED was noted at 3 h post-exercise/feeding (P = 0.014). Rictor/WGA colocalization remained unaltered throughout the trial. Alterations in mTORC1 cellular location coincided with elevated S6K1 kinase activity, which rose to a greater extent in EXFED compared with FED at 1 h post-exercise/feeding (P < 0.001), and only remained elevated in EXFED at the 3 h time point (P = 0.037). Collectively these data suggest that mTORC1 redistribution within the cell is a fundamental response to resistance exercise and feeding, whereas mTORC2 is predominantly situated at the sarcolemma and does not alter localization.