Omega‐3 (n‐3) fatty acid supplementation enhances muscle protein synthesis and muscle size. Whether n‐3 fatty acid supplementation attenuates human muscle disuse atrophy is unknown. We determined the influence of n‐3 fatty acid supplementation on muscle size, mass, and integrated rates of myofibrillar protein synthesis (MyoPS) following 2 wk of muscle disuse and recovery in women. Twenty women (BMI = 23.0 ± 2.3 kg/m2, age = 22 ± 3 yr) underwent 2 wk of unilateral limb immobilization followed by 2 wk of return to normal activity. Starting 4 wk prior to immobilization, participants consumed either 5 g/d of n‐3 fatty acid or an isoenergetic quantity of sunflower oil (control). Muscle size and mass were measured pre‐ and postimmobilization, and after recovery. Serial muscle biopsies were obtained to measure integrated (daily) MyoPS. Following immobilization, the decline in muscle volume was greater in the control group compared to the n‐3 fatty acid group (14 vs. 8%, P < 0.05) and was not different from preimmobilization at recovery in the n‐3 fatty acid group; however, it was still lower in the control group (P < 0.05). Muscle mass was reduced in the control group only (P < 0.05). MyoPS was higher in the n‐3 group compared with the control group at all times (P < 0.05). We conclude that n‐3 fatty acid supplementation attenuates skeletal muscle disuse atrophy in young women, which may be mediated by higher rates of MyoPS.—McGlory, C., Gorissen, S. H. M., Kamal, M., Bahniwal, R., Hector, A. J., Baker, S. K., Chabowski, A., Phillips, S. M. Omega‐3 fatty acid supplementation attenuates skeletal muscle disuse atrophy during two weeks of unilateral leg immobilization in healthy young women. FASEB J. 33, 4586–4597 (2019). http://www.fasebj.org

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 &lt; 0.01), whereas CP increased MPS only in Exercise (0.012 ± 0.013%/h) (P &lt; 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 &lt; 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 &lt; 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.

Omega‐3 (ω‐3) supplementation attenuates immobilization‐induced atrophy; however, the underlying mechanisms remain unclear. Since mitochondrial dysfunction and oxidative stress have been implicated in muscle atrophy, we examined whether ω‐3 supplementation could mitigate disuse‐mediated mitochondrial dysfunction. Healthy young women (age = 22 ± 3 yr) randomly received control (n = 9) or ω‐3 supplementation (n = 11; 3 g eicosapentaenoic acid, 2 g docosahexaenoic acid) for 4 wk prior to and throughout 2 wk of single‐limb immobilization. Biopsies were performed before and after 3 and 14 d of immobilization for the assessment of mitochondrial respiration, H2O2 emission, and markers of ADP transport/lipid metabolism. In controls, immobilization rapidly (3 d) reduced (∼20%) ADP‐stimulated mitochondrial respiration without altering ADP sensitivity or the abundance of mitochondrial proteins. Extending immobilization to 14 d did not further reduce mitochondrial coupled respiration; however, unlike following 3 d, mitochondrial proteins were reduced ∼20%. In contrast, ω‐3 supplementation prevented immobilization‐induced reductions in mitochondrial content and respiration throughout the immobilization period. Regardless of dietary supplement, immobilization did not alter mitochondrial H2O2 emission in the presence or absence of ADP, markers of cellular redox state, mitochondrial lipid–supported respiration, or lipid‐related metabolic proteins. These data highlight the rapidity of mitochondrial adaptations in response to muscle disuse, challenge the necessity for increased oxidative stress during inactivity, and establish that ω‐3 supplementation preserves oxidative phosphorylation function and content during immobilization.—Miotto, P. M., McGlory, C., Bahniwal, R., Kamal, M., Phillips, S. M., Holloway, G. P. Supplementation with dietary ω‐3 mitigates immobilization‐induced reductions in skeletal muscle mitochondrial respiration in young women. FASEB J. 33, 8232–8240 (2019). http://www.fasebj.org

Factors influencing inter-individual variability of responses to resistance training(RT) remain to be fully elucidated. We have proposed the importance of capillarization in skeletal muscle for the satellite cell (SC) response to RT-induced muscle hypertrophy, and hypothesized that aerobic conditioning (AC) would augment RT-induced adaptations. Fourteen healthy young (22 ± 2 years) men and women underwent AC via 6 weeks of unilateral cycling followed by 10 weeks of bilateral RT to investigate how AC alters SC content, activity, and muscle hypertrophy following RT. Muscle biopsies were taken at baseline (unilateral), post AC (bilateral), and post RT (bilateral) in the aerobically conditioned (AC + RT) and unconditioned (RT) legs. Immunofluorescence was used to determine muscle capillarization, fiber size, SC content, and activity. Type I and type II fiber cross-sectional area (CSA) increased following RT, and when legs were analyzed independently, AC + RT increased type I, type II, and mixed-fiber CSA, where the RT leg tended to increase type II (p = .05), but not type I or mixed-fiber CSA. SC content, activation, and differentiation increased with RT, where type I total and quiescent SC content was greater in AC + RT compared to the RT leg. Those with the greatest capillary-to-fiber perimeter exchange index before RT had the greatest change in CSA following RT and a significant relationship was observed between type II fiber capillarization and the change in type II-fiber CSA with RT (r = 0.35). This study demonstrates that AC prior to RT can augment RT-induced muscle adaptions and that these differences are associated with increases in capillarization.

Skeletal muscle has a high capacity to repair and remodel in response to damage, largely through the action of resident muscle stem cells, termed satellite cells. Satellite cells are required for the proper repair of skeletal muscle through a process known as myogenesis. Recent investigations have observed relationships between satellite cells and other cell types and structures within the muscle microenvironment. These findings suggest that the crosstalk between inflammatory cells, fibrogenic cells, bone-marrow-derived cells, satellite cells, and the vasculature is essential for the restoration of muscle homeostasis. This review will discuss the influence of the cells and structures within the muscle microenvironment on satellite cell function and muscle repair.