Postexercise muscle glycogen resynthesis in humans

Since the pioneering studies conducted in the 1960s in which glycogen status was investigated using the muscle biopsy technique, sports scientists have developed a sophisticated appreciation of the role of glycogen in cellular adaptation and exercise performance, as well as sites of storage of this important metabolic fuel. While sports nutrition guidelines have evolved during the past decade to incorporate sport-specific and periodized manipulation of carbohydrate (CHO) availability, athletes attempt to maximize muscle glycogen synthesis between important workouts or competitive events so that fuel stores closely match the demands of the prescribed exercise. Therefore, it is important to understand the factors that enhance or impair this biphasic process. In the early postexercise period (0–4 h), glycogen depletion provides a strong drive for its own resynthesis, with the provision of CHO (~1 g/kg body mass) optimizing this process. During the later phase of recovery (4–24 h), CHO intake should meet the anticipated fuel needs of the training/competition, with the type, form, and pattern of intake being less important than total intake. Dietary strategies that can enhance glycogen synthesis from suboptimal amounts of CHO or energy intake are of practical interest to many athletes; in this scenario, the coingestion of protein with CHO can assist glycogen storage. Future research should identify other factors that enhance the rate of synthesis of glycogen storage in a limited time frame, improve glycogen storage from a limited CHO intake, or increase muscle glycogen supercompensation

Neuromuscular electrical stimulation prevents muscle wasting in critically ill comatose patients

This is the author accepted manuscript. The final version is available from Portland Press via the DOI in this recordFully sedated patients, being treated in the intensive care unit (ICU), experience substantial skeletal muscle loss. Consequently, survival rate is reduced and full recovery after awakening is compromised. Neuromuscular electrical stimulation (NMES) represents an effective method to stimulate muscle protein synthesis and alleviate muscle disuse atrophy in healthy subjects. We investigated the efficacy of twice-daily NMES to alleviate muscle loss in six fully sedated ICU patients admitted for acute critical illness [n=3 males, n=3 females; age 63 ± 6 y; APACHE II (Acute Physiology and Chronic Health Evaluation II) disease-severity-score: 29 ± 2]. One leg was subjected to twice-daily NMES of the quadriceps muscle for a period of 7 ± 1 day whereas the other leg acted as a non-stimulated control (CON). Directly before the first and on the morning after the final NMES session, quadriceps muscle biopsies were collected from both legs to assess muscle fibre-type-specific cross-sectional area (CSA). Furthermore, phosphorylation status of the key proteins involved in the regulation of muscle protein synthesis was assessed and mRNA expression of selected genes was measured. In the CON leg, type 1 and type 2 muscle-fibre-CSA decreased by 16 ± 9% and 24 ± 7% respectively (P<0.05). No muscle atrophy was observed in the stimulated leg. NMES increased mammalian target of rapamycin (mTOR) phosphorylation by 19 ± 5% when compared with baseline (P<0.05), with no changes in the CON leg. Furthermore, mRNA expression of key genes involved in muscle protein breakdown either declined [forkhead box protein O1 (FOXO1); P<0.05] or remained unchanged [muscle atrophy F-box (MAFBx) and muscle RING-finger protein-1 (MuRF1)], with no differences between the legs. In conclusion, NMES represents an effective and feasible interventional strategy to prevent skeletal muscle atrophy in critically ill comatose patients

Age-Associated Impairments in Mitochondrial ADP Sensitivity Contribute to Redox Stress in Senescent Human Skeletal Muscle.

This is the final version of the article. Available from Elsevier (Cell Press) via the DOI in this record.It remains unknown if mitochondrial bioenergetics are altered with aging in humans. We established an in vitro method to simultaneously determine mitochondrial respiration and H2O2emission in skeletal muscle tissue across a range of biologically relevant ADP concentrations. Using this approach, we provide evidence that, although the capacity for mitochondrial H2O2emission is not increased with aging, mitochondrial ADP sensitivity is impaired. This resulted in an increase in mitochondrial H2O2and the fraction of electron leak to H2O2, in the presence of virtually all ADP concentrations examined. Moreover, although prolonged resistance training in older individuals increased muscle mass, strength, and maximal mitochondrial respiration, exercise training did not alter H2O2emission rates in the presence of ADP, the fraction of electron leak to H2O2, or the redox state of the muscle. These data establish that a reduction in mitochondrial ADP sensitivity increases mitochondrial H2O2emission and contributes to age-associated redox stress.This work was funded by the Natural Sciences and Engineering Research Council of Canada (03656) and TI Food and Nutrition, a public-private partnership on precompetitive research in food and nutrition

Skeletal muscle disuse atrophy is not attenuated by dietary protein supplementation in healthy older men

This is the author accepted manuscript. The final version is available from OUP via the DOI in this recordShort successive periods of muscle disuse, due to injury or illness, can contribute significantly to the loss of muscle mass with aging (sarcopenia). It has been suggested that increasing the protein content of the diet may be an effective dietary strategy to attenuate muscle disuse atrophy. We hypothesized that protein supplementation twice daily would preserve muscle mass during a short period of limb immobilization. Twenty-three healthy older (69 ± 1 y) men were subjected to 5 d of one-legged knee immobilization by means of a full-leg cast with (PRO group; n = 11) or without (CON group; n = 12) administration of a dietary protein supplement (20.7 g of protein, 9.3 g of carbohydrate, and 3.0 g of fat) twice daily. Two d prior to and immediately after the immobilization period, single-slice computed tomography scans of the quadriceps and single-leg 1 repetition maximum strength tests were performed to assess muscle cross-sectional area (CSA) and leg muscle strength, respectively. Additionally, muscle biopsies were collected to assess muscle fiber characteristics as well as mRNA and protein expression of selected genes. Immobilization decreased quadriceps' CSAs by 1.5 ± 0.7% (P < 0.05) and 2.0 ± 0.6% (P < 0.05), and muscle strength by 8.3 ± 3.3% (P < 0.05) and 9.3 ± 1.6% (P < 0.05) in the CON and PRO groups, respectively, without differences between groups. Skeletal muscle myostatin, myogenin, and muscle RING-finger protein-1 (MuRF1) mRNA expression increased following immobilization in both groups (P < 0.05), whereas muscle atrophy F-box/atrogen-1 (MAFBx) mRNA expression increased in the PRO group only (P < 0.05). In conclusion, dietary protein supplementation (∼20 g twice daily) does not attenuate muscle loss during short-term muscle disuse in healthy older men. This trial was registered at clinicaltrials.gov as NCT01588808

Neuromuscular electrical stimulation prevents muscle disuse atrophy during leg immobilization in humans

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordAIM: Short periods of muscle disuse, due to illness or injury, result in substantial skeletal muscle atrophy. Recently, we have shown that a single session of neuromuscular electrical stimulation (NMES) increases muscle protein synthesis rates. The aim was to investigate the capacity for daily NMES to attenuate muscle atrophy during short-term muscle disuse. METHODS: Twenty-four healthy, young (23 ± 1 year) males participated in the present study. Volunteers were subjected to 5 days of one-legged knee immobilization with (NMES; n = 12) or without (CON; n = 12) supervised NMES sessions (40-min sessions, twice daily). Two days prior to and immediately after the immobilization period, CT scans and single-leg one-repetition maximum (1RM) strength tests were performed to assess quadriceps muscle cross-sectional area (CSA) and leg muscle strength respectively. Furthermore, muscle biopsies were taken to assess muscle fibre CSA, satellite cell content and mRNA and protein expression of selected genes. RESULTS: In CON, immobilization reduced quadriceps CSA by 3.5 ± 0.5% (P < 0.0001) and muscle strength by 9 ± 2% (P < 0.05). In contrast, no significant muscle loss was detected following immobilization in NMES although strength declined by 7 ± 3% (P < 0.05). Muscle MAFbx and MuRF1 mRNA expression increased following immobilization in CON (P < 0.001 and P = 0.07 respectively), whereas levels either declined (P < 0.01) or did not change in NMES, respectively. Immobilization led to an increase in muscle myostatin mRNA expression in CON (P < 0.05), but remained unchanged in NMES. CONCLUSION: During short-term disuse, NMES represents an effective interventional strategy to prevent the loss of muscle mass, but it does not allow preservation of muscle strength. NMES during disuse may be of important clinical relevance in both health and disease

Aging Is Accompanied by a Blunted Muscle Protein Synthetic Response to Protein Ingestion.

Published onlineJournal ArticleThis is the final version of the article. Available from Public Library of Science via the DOI in this record.PURPOSE: Progressive loss of skeletal muscle mass with aging (sarcopenia) forms a global health concern. It has been suggested that an impaired capacity to increase muscle protein synthesis rates in response to protein intake is a key contributor to sarcopenia. We assessed whether differences in post-absorptive and/or post-prandial muscle protein synthesis rates exist between large cohorts of healthy young and older men. PROCEDURES: We performed a cross-sectional, retrospective study comparing in vivo post-absorptive muscle protein synthesis rates determined with stable isotope methodologies between 34 healthy young (22±1 y) and 72 older (75±1 y) men, and post-prandial muscle protein synthesis rates between 35 healthy young (22±1 y) and 40 older (74±1 y) men. FINDINGS: Post-absorptive muscle protein synthesis rates did not differ significantly between the young and older group. Post-prandial muscle protein synthesis rates were 16% lower in the older subjects when compared with the young. Muscle protein synthesis rates were >3 fold more responsive to dietary protein ingestion in the young. Irrespective of age, there was a strong negative correlation between post-absorptive muscle protein synthesis rates and the increase in muscle protein synthesis rate following protein ingestion. CONCLUSIONS: Aging is associated with the development of muscle anabolic inflexibility which represents a key physiological mechanism underpinning sarcopenia

Intermittent versus continuous enteral nutrition attenuates increases in insulin and leptin during short-term bed rest

This is the final version. Available on open access from Springer via the DOI in this recordPurpose: To compare endocrine responses to intermittent vs continuous enteral nutrition provision during short-term bed rest. Methods: Twenty healthy men underwent 7 days of bed rest, during which they were randomized to receive enteral nutrition (47%E as carbohydrate, 34%E as fat, 16%E as protein and 3%E as fibre) in a continuous (CONTINUOUS; n = 10; 24 h day−1 at a constant rate) or intermittent (INTERMITTENT; n = 10; as 4 meals per day separated by 5 h) pattern. Daily plasma samples were taken every morning to assess metabolite/hormone concentrations. Results: During bed rest, plasma leptin concentrations were elevated to a lesser extent with INTERMITTENT vs CONTINUOUS (iAUC: 0.42 ± 0.38 vs 0.95 ± 0.48 nmol L−1, respectively; P = 0.014) as were insulin concentrations (interaction effect, P < 0.001) which reached a peak of 369 ± 225 pmol L−1 in CONTINUOUS, compared to 94 ± 38 pmol L−1 in INTERMITTENT (P = 0.001). Changes in glucose infusion rate were positively correlated with changes in fasting plasma GLP-1 concentrations (r = 0.44, P = 0.049). Conclusion: Intermittent enteral nutrition attenuates the progressive rise in plasma leptin and insulinemia seen with continuous feeding during bed rest, suggesting that continuous feeding increases insulin requirements to maintain euglycemia. This raises the possibility that hepatic insulin sensitivity is impaired to a greater extent with continuous versus intermittent feeding during bed rest. To attenuate endocrine and metabolic changes with enteral feeding, an intermittent feeding strategy may, therefore, be preferable to continuous provision of nutrition. This trial was registered on clinicaltrials.gov as NCT02521025.University of Bat

There Are No Nonresponders to Resistance-Type Exercise Training in Older Men and Women

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordOBJECTIVE: To assess the proposed prevalence of unresponsiveness of older men and women to augment lean body mass, muscle fiber size, muscle strength, and/or physical function following prolonged resistance-type exercise training. DESIGN/SETTING/PARTICIPANTS: A retrospective analysis of the adaptive response to 12 (n = 110) and 24 (n = 85) weeks of supervised resistance-type exercise training in older (>65 years) men and women. MEASUREMENTS: Lean body mass (DXA), type I and type II muscle fiber size (biopsy), leg strength (1-RM on leg press and leg extension), and physical function (chair-rise time) were assessed at baseline, and after 12 and 24 weeks of resistance-type exercise training. RESULTS: Lean body mass increased by 0.9 ± 0.1 kg (range: -3.3 to +5.4 kg; P < .001) from 0 to 12 weeks of training. From 0 to 24 weeks, lean body mass increased by 1.1 ± 0.2 kg (range: -1.8 to +9.2 kg; P < .001). Type I and II muscle fiber size increased by 324 ± 137 μm(2) (range: -4458 to +3386 μm(2); P = .021), and 701 ± 137 μm(2) (range: -4041 to +3904 μm(2); P < .001) from 0 to 12 weeks. From 0 to 24 weeks, type I and II muscle fiber size increased by 360 ± 157 μm(2) (range: -3531 to +3426 μm(2); P = .026) and 779 ± 161 μm(2) (range: -2728 to +3815 μm(2); P < .001). The 1-RM strength on the leg press and leg extension increased by 33 ± 2 kg (range: -36 to +87 kg; P < .001) and 20 ± 1 kg (range: -22 to +56 kg; P < .001) from 0 to 12 weeks. From 0 to 24 weeks, leg press and leg extension 1-RM increased by 50 ± 3 kg (range: -28 to +145 kg; P < .001) and 29 ± 2 kg (range: -19 to +60 kg; P < .001). Chair-rise time decreased by 1.3 ± 0.4 seconds (range: +21.6 to -12.5 seconds; P = .003) from 0 to 12 weeks. From 0 to 24 weeks, chair-rise time decreased by 2.3 ± 0.4 seconds (range: +10.5 to -23.0 seconds; P < .001). Nonresponsiveness was not apparent in any subject, as a positive adaptive response on at least one training outcome was apparent in every subject. CONCLUSIONS: A large heterogeneity was apparent in the adaptive response to prolonged resistance-type exercise training when changes in lean body mass, muscle fiber size, strength, and physical function were assessed in older men and women. The level of responsiveness was strongly affected by the duration of the exercise intervention, with more positive responses following more prolonged exercise training. We conclude that there are no nonresponders to the benefits of resistance-type exercise training on lean body mass, fiber size, strength, or function in the older population. Consequently, resistance-type exercise should be promoted without restriction to support healthy aging in the older population.This work was funded by TI Food and Nutrition, a public-private partnership on precompetitive research in food and nutrition

Temporal Muscle-Specific Disuse Atrophy during One Week of Leg Immobilization

This is the author accepted manuscript. The final version is available from Wolters Kluwer via the DOI in this recordPurpose Musculoskeletal injuries necessitate periods of disuse (i.e. limb immobilization) during which rapid skeletal muscle atrophy occurs. The relative susceptibility of different muscles of the thigh to disuse atrophy remains uninvestigated. We assessed muscle disuse atrophy of individual thigh muscles throughout one week of unilateral knee immobilization. Methods Thirteen healthy, young (20.2±0.6 y) men underwent 7 days of unilateral leg immobilization via knee bracing. MRI scans were performed bilaterally prior to, and following 2 and 7 days of immobilization to determine the volume and anatomical cross-sectional area (aCSA) of the individual muscle groups of the upper legs. Results In contrast to the control leg, total thigh muscle volume had decreased by 1.7±0.3 (P<0.01) and 5.5±0.6% (P<0.001) in the immobilized leg after 2 and 7 days of disuse, respectively. Muscle loss was significantly greater in the M. quadriceps (day 2; 1.7±0.3 (P<0.05) and day 7; 6.7±0.6%) when compared with the M. hamstrings (day 2; 1.4±0.2% (P<0.01) and day 7; 3.5±0.3%) following 7 days of disuse (P<0.001). Individual muscles of the thigh exhibited different atrophy rates with the M. vastus lateralis aCSA showing the greater (2.6±0.4 and 7.2±0.8%), and the M. gracilis the lesser (1.1±0.7 and 2.3±1.0%) decline following 2 and 7 days of immobilization, respectively (P<0.01). Conclusion Thigh muscle disuse atrophy occurs rapidly and is already evident within 2 days of leg immobilization and progresses at a similar rate over the next 5 days (~0.8% muscle loss per day). M. quadriceps muscle shows more atrophy when compared with the M. hamstrings.University of MaastrichtRoyal SocietyUniversity of ExeterNational Institute for Health Research (NIHR