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Leucine Supplementation Increases Muscle Strength and Volume, Reduces Inflammation, and Affects Wellbeing in Adults and Adolescents with Cerebral Palsy.
Theis, N, Brown, MA, Wood, P, Waldron, M
The Journal of nutrition. 2021;(1):59-64
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Abstract
BACKGROUND Spastic cerebral palsy (CP) is characterized by muscle weakness owing, in part, to a blunted muscle protein synthetic response. This might be normalized by long-term leucine supplementation. OBJECTIVES The study assessed the effects of 10 wk leucine supplementation in adolescents and adults with CP. METHODS The study was a single-center randomized controlled trial. Twenty-four participants were randomly assigned to a control group (n = 12) or a leucine group (n = 12). l-Leucine (192 mg/kg body mass) was dissolved in water and administered daily for 10 wk. The primary outcome measures of elbow flexor muscle strength and muscle volume (measured by 3D ultrasound technique) and inflammation [C-reactive protein (CRP) concentration] were assessed before and after the 10 wk, alongside the secondary outcomes of body composition (measured by CP-specific skinfold assessment), metabolic rate (measured by indirect calorimetry), and wellbeing (measured by a self-reported daily questionnaire). Data were compared via a series of 2-factor mixed ANOVAs. RESULTS Twenty-one participants completed the intervention (control group: n = 11, mean ± SD age: 18.3 ± 2.8 y, body mass: 48.8 ± 11.9 kg, 45% male; leucine group: n = 10, age: 18.6 ± 1.7 y, body mass: 58.3 ± 20.2 kg, 70% male). After 10 wk, there was a 25.4% increase in strength (P = 0.019) and a 3.6% increase in muscle volume (P = 0.001) in the leucine group, with no changes in the control group. This was accompanied by a 59.1% reduction in CRP (P = 0.045) and improved perceptions of wellbeing (P = 0.006) in the leucine group. No changes in metabolism or body composition were observed in either group (P > 0.05). CONCLUSIONS Improvements in muscle strength and volume with leucine supplementation might provide important functional changes for adults and adolescents with CP and could be partly explained by reduced inflammation. The improved wellbeing highlights its capacity to improve the quality of daily living. This trial was registered at clinicaltrials.gov as NCT03668548.
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Impact of protein supplementation during endurance training on changes in skeletal muscle transcriptome.
Knuiman, P, Hangelbroek, R, Boekschoten, M, Hopman, M, Mensink, M
BMC genomics. 2020;(1):397
Abstract
BACKGROUND Protein supplementation improves physiological adaptations to endurance training, but the impact on adaptive changes in the skeletal muscle transcriptome remains elusive. The present analysis was executed to determine the impact of protein supplementation on changes in the skeletal muscle transcriptome following 5-weeks of endurance training. RESULTS Skeletal muscle tissue samples from the vastus lateralis were taken before and after 5-weeks of endurance training to assess changes in the skeletal muscle transcriptome. One hundred and 63 genes were differentially expressed after 5-weeks of endurance training in both groups (q-value< 0.05). In addition, the number of genes differentially expressed was higher in the protein group (PRO) (892, q-value< 0.05) when compared with the control group (CON) (440, q-value< 0.05), with no time-by-treatment interaction effect (q-value> 0.05). Endurance training primarily affected expression levels of genes related to extracellular matrix and these changes tended to be greater in PRO than in CON. CONCLUSIONS Protein supplementation subtly impacts endurance training-induced changes in the skeletal muscle transcriptome. In addition, our transcriptomic analysis revealed that the extracellular matrix may be an important factor for skeletal muscle adaptation in response to endurance training. This trial was registered at clinicaltrials.gov as NCT03462381, March 12, 2018. TRIAL REGISTRATION This trial was registered at clinicaltrials.gov as NCT03462381.
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Higher Muscle Mass Implies Increased Free-Thyroxine to Free-Triiodothyronine Ratio in Subjects With Overweight and Obesity.
Zupo, R, Castellana, F, Sardone, R, Lampignano, L, Paradiso, S, Giagulli, VA, Triggiani, V, Di Lorenzo, L, Giannelli, G, De Pergola, G
Frontiers in endocrinology. 2020;:565065
Abstract
UNLABELLED Thyroid hormones control both metabolic pathways and body composition, whereas little knowledge is available about the possible influence of skeletal muscle mass (MM) on thyroid hormone metabolism and circulating levels. This was a cross-sectional study conducted at the Population Health Unit of the National Institute of Gastroenterology IRCCS "S. de Bellis" (Italy) and investigating the extent to which skeletal MM affects thyroid function in obesity. Two hundred twenty-seven consecutive healthy volunteers (155 women and 72 men) with overweight and obesity (BMI ≥ 25 kg/m2) and taking no medication or supplement were assessed for hormone, metabolic and routine laboratory parameters. Body composition parameters were collected by using bioelectrical impedance analysis (BIA). MM was directly related to the body mass index (BMI), waist circumference (WC), insulin, triglycerides, uric acid and free-triiodothyronine (FT3) serum levels, FT3 to the free-thyroxine (FT4) ratio, and insulin-resistance (HOMA-IR), and inversely related to age, total, and HDL-cholesterol serum levels. Multiple regression models confirmed the relationship between MM and the FT3 to FT4 ratio, independently of age, BMI, TSH, triglycerides, and insulin serum levels. The same analyses run by gender showed that this relationship maintained significance only in men. Increased skeletal MM in obesity results in improved thyroid activity mediated by increased T4 conversion to T3, and higher FT3 circulating levels, particularly in men. In conclusion, preserving a greater skeletal MM in obesity helps to enhance thyroid activity. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, identifier NCT04327375.
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RaceRunning training improves stamina and promotes skeletal muscle hypertrophy in young individuals with cerebral palsy.
Hjalmarsson, E, Fernandez-Gonzalo, R, Lidbeck, C, Palmcrantz, A, Jia, A, Kvist, O, Pontén, E, von Walden, F
BMC musculoskeletal disorders. 2020;(1):193
Abstract
BACKGROUND Individuals with cerebral palsy (CP) are less physically active, spend more time sedentary and have lower cardiorespiratory endurance as compared to typically developed individuals. RaceRunning enables high-intensity exercise in individuals with CP with limited or no walking ability, using a three-wheeled running bike with a saddle and a chest plate for support, but no pedals. Training adaptations using this type of exercise are unknown. METHODS Fifteen adolescents/young adults (mean age 16, range 9-29, 7 females/8 males) with CP completed 12 weeks, two sessions/week, of RaceRunning training. Measurements of cardiorespiratory endurance (6-min RaceRunning test (6-MRT), average and maximum heart rate, rate of perceived exertion using the Borg scale (Borg-RPE)), skeletal muscle thickness (ultrasound) of the thigh (vastus lateralis and intermedius muscles) and lower leg (medial gastrocnemius muscle) and passive range of motion (pROM) of hip, knee and ankle were collected before and after the training period. RESULTS Cardiorespiratory endurance increased on average 34% (6-MRT distance; pre 576 ± 320 m vs. post 723 ± 368 m, p < 0.001). Average and maximum heart rate and Borg-RPE during the 6-MRT did not differ pre vs. post training. Thickness of the medial gastrocnemius muscle increased 9% in response to training (p < 0.05) on the more-affected side. Passive hip flexion increased (p < 0.05) on the less-affected side and ankle dorsiflexion decreased (p < 0.05) on the more affected side after 12 weeks of RaceRunning training. CONCLUSIONS These results support the efficacy of RaceRunning as a powerful and effective training modality in individuals with CP, promoting both cardiorespiratory and peripheral adaptations.
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Magnesium transport and homeostasis-related gene expression in skeletal muscle of young and old adults: analysis of the transcriptomic data from the PROOF cohort Study.
Coudy-Gandilhon, C, Gueugneau, M, Taillandier, D, Combaret, L, Polge, C, Roche, F, Barthélémy, JC, Féasson, L, Maier, JA, Mazur, A, et al
Magnesium research. 2019;(3):72-82
Abstract
Magnesium (Mg2+) is critical for a number of biological processes and 25% body Mg2+ is located in the skeletal muscle. Mg2+ transport and homeostasis systems (MgTHs) regulate intracellular Mg2+ concentration and muscle MgTHs are thus related to whole body Mg2+ homeostasis. Nonetheless, few studies have investigated the regulation of muscle MgTHs under (patho)physiological conditions. Herein, we assessed the relationship between the expression of MgTHs genes (Trpm6, Trpm7, Magt1, Mrs2, Cnnm1-4, Slc41a1-3) and relevant pathways in human sarcopenia, which is one of the most dramatic physiologic changes affecting the human body. Transcriptomic data were compared between young adult (YO, 22 y, n = 11) and old (EL, 73 y, n = 13) men from the PROOF cohort. MgTH mRNA levels did not change with aging, with the exception of a slight decrease for Slc41a3. Nevertheless, interindividual variations of mRNA levels revealed strong correlations between MgTHs in the YO group, while few were maintained in the EL muscle. Moreover, in the YO muscle, different clusters of MgTH mRNAs strongly correlated with divers physiological (BMI, blood pressure) and muscle characteristics (intramyocellular droplets, capillarization); however, most correlations changed or disappeared in the EL muscle. Further investigations of the whole transcriptome identified several sets of mRNAs correlated with defined MgTHs. There again was a sharp difference between YO and EL muscles, as the number of mRNAs correlated with MgTHs strongly decreased with aging. Gene ontology analyses of these sets of correlated mRNAs revealed 6 biological processes common to YO and EL, 3 specific to the YO (RNA processing, translation, respiration), and 2 (regulation of catabolic process, Wnt signaling) to the EL muscle. Overall, these observations lead to questions about potential resilience to muscle Mg2+ homeostasis in the elderly.
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Home-hit improves muscle capillarisation and eNOS/NAD(P)Hoxidase protein ratio in obese individuals with elevated cardiovascular disease risk.
Scott, SN, Shepherd, SO, Hopkins, N, Dawson, EA, Strauss, JA, Wright, DJ, Cooper, RG, Kumar, P, Wagenmakers, AJM, Cocks, M
The Journal of physiology. 2019;(16):4203-4225
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Abstract
KEY POINTS Obesity and sedentary behaviour are associated with capillary rarefaction and impaired muscle microvascular vasoreactivity, due to reduced nitric oxide bioavailability. Low-volume high-intensity interval training (HIT) is a time-efficient alternative to traditional moderate-intensity continuous training (MICT), but its effect on the muscle microvasculature has not been studied. The applicability of current laboratory- and gym-based HIT protocols for obese individuals with low fitness and mobility has been disputed by public health experts, who cite the strenuous nature and complex protocols as major barriers. Therefore, we developed a virtually supervised HIT protocol targeting this group that can be performed at home without equipment (Home-HIT). This study is the first to show that 12 weeks of virtually supervised Home-HIT in obese individuals with elevated cardiovascular disease risk leads to similar increases in capillarisation and eNOS/NAD(P)Hoxidase protein ratio within the muscle microvascular endothelium as virtually supervised home-based MICT and laboratory-based HIT, while reducing many of the major barriers to exercise. ABSTRACT This study investigated the effect of a novel virtually supervised home-based high-intensity interval training (HIT) (Home-HIT) intervention in obese individuals with elevated cardiovascular disease (CVD) risk on capillarisation and muscle microvascular eNOS/NAD(P)Hoxidase ratio. Thirty-two adults with elevated CVD risk (age 36 ± 10 years; body mass index 34.3 ± 5 kg m-2 ; V̇O2peak 24.6 ± 5.7 ml kg min-1 ), completed one of three 12-week training programmes: Home-HIT (n = 9), laboratory-based supervised HIT (Lab-HIT; n = 10) or virtually supervised home-based moderate-intensity continuous training (Home-MICT; n = 13). Muscle biopsies were taken before and after training to assess changes in vascular enzymes, capillarisation, mitochondrial density, intramuscular triglyceride content and GLUT4 protein expression using quantitative immunofluorescence microscopy. Training increased V̇O2peak (P < 0.001), whole-body insulin sensitivity (P = 0.033) and flow-mediated dilatation (P < 0.001), while aortic pulse wave velocity decreased (P < 0.001) in all three groups. Immunofluorescence microscopy revealed comparable increases in total eNOS content in terminal arterioles and capillaries (P < 0.001) in the three conditions. There was no change in eNOS ser1177 phosphorylation (arterioles P = 0.802; capillaries P = 0.311), but eNOS ser1177 /eNOS content ratio decreased significantly following training in arterioles and capillaries (P < 0.001). Training decreased NOX2 content (arterioles P < 0.001; capillaries P < 0.001), but there was no change in p47phox content (arterioles P = 0.101; capillaries P = 0.345). All measures of capillarisation increased (P < 0.05). There were no between-group differences. Despite having no direct supervision during exercise, virtually supervised Home-HIT resulted in comparable structural and endothelial enzymatic changes in the skeletal muscle microvessels to the traditional training methods. We provide strong evidence that Home-HIT is an effective novel strategy to remove barriers to exercise and improve health in an obese population at risk of CVD.
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Redundancy in regulation of lipid accumulation in skeletal muscle during prolonged fasting in obese men.
Høgild, ML, Gudiksen, A, Pilegaard, H, Stødkilde-Jørgensen, H, Pedersen, SB, Møller, N, Jørgensen, JOL, Jessen, N
Physiological reports. 2019;(21):e14285
Abstract
Fasting in human subjects shifts skeletal muscle metabolism toward lipid utilization and accumulation, including intramyocellular lipid (IMCL) deposition. Growth hormone (GH) secretion amplifies during fasting and promotes lipolysis and lipid oxidation, but it is unknown to which degree lipid deposition and metabolism in skeletal muscle during fasting depends on GH action. To test this, we studied nine obese but otherwise healthy men thrice: (a) in the postabsorptive state ("CTRL"), (b) during 72-hr fasting ("FAST"), and (c) during 72-hr fasting and treatment with a GH antagonist (GHA) ("FAST + GHA"). IMCL was assessed by magnetic resonance spectroscopy (MRS) and blood samples were drawn for plasma metabolomics assessment while muscle biopsies were obtained for measurements of regulators of substrate metabolism. Prolonged fasting was associated with elevated GH levels and a pronounced GHA-independent increase in circulating medium- and long-chain fatty acids, glycerol, and ketone bodies indicating increased supply of lipid intermediates to skeletal muscle. Additionally, fasting was associated with a release of short-, medium-, and long-chain acylcarnitines to the circulation from an increased β-oxidation. This was consistent with a ≈55%-60% decrease in pyruvate dehydrogenase (PDHa) activity. Opposite, IMCL content increased ≈75% with prolonged fasting without an effect of GHA. We suggest that prolonged fasting increases lipid uptake in skeletal muscle and saturates lipid oxidation, both favoring IMCL deposition. This occurs without a detectable effect of GHA on skeletal muscle lipid metabolism.
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Effect of High-Intensity Exercise on Multiple Sclerosis Function and Phosphorous Magnetic Resonance Spectroscopy Outcomes.
Orban, A, Garg, B, Sammi, MK, Bourdette, DN, Rooney, WD, Kuehl, K, Spain, RI
Medicine and science in sports and exercise. 2019;(7):1380-1386
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Abstract
PURPOSE We determined if a high-intensity aerobic exercise program would be safe, improve expected fitness and clinical outcomes, and alter exploratory phosphorous magnetic resonance spectroscopy (P MRS) outcomes in persons with multiple sclerosis (PwMS). METHODS This open-label prospective pilot study compared two cohorts of ambulatory PwMS matched for age, sex and V˙O2max. Cohorts underwent 8 wk of high-intensity aerobic exercise (MS-Ex, n = 10) or guided stretching (MS-Ctr, n = 7). Aerobic exercise consisted of four 30-min sessions per week while maintaining ≥70% maximal HR. Changes in cardiorespiratory fitness, clinical outcomes, and P MRS of tibialis anterior (TA) muscle and brain were compared. Cross-sectional P MRS comparisons were made between all MS participants and a separate matched healthy control population. RESULTS The MS-Ex cohort achieved target increases in V˙O2max (mean, +12.7%; P = <0.001, between-group improvement, P = 0.03). One participant was withdrawn for exercise-induced syncope. The MS-Ex cohort had within-group improvements in fat mass (-5.8%; P = 0.04), lean muscle mass (+2.6%; P = 0.02), Symbol Digit Modalities Test (+15.1%; P = 0.04), and cognitive subscore of the Modified Fatigue Impact Scale (-26%; P = 0.03), whereas only the physical subscore of the Modified Fatigue Impact Scale improved in MS-Ctr (-16.1%; P = 0.007). P MRS revealed significant within-group increases in MS-Ex participants in TA rate constant of phosphocreatine (PCr) recovery (+31.5%; P = 0.03) and adenosine triphosphate/PCr (+3.2%; P = 0.01), and near significant between-group increases in TA PCr recovery rate constant (P = 0.05) but no significant changes in brain P MRS after exercise. Cross-sectional differences existed between MS and healthy control brain PCr/inorganic phosphate (4.61 ± 0.44, 3.93 ± 0.19; P = 0.0019). CONCLUSIONS High-intensity aerobic exercise in PwMS improved expected cardiorespiratory and clinical outcomes but provoked one serious adverse event. The P MRS may serve to explore underlying mechanisms by which aerobic exercise exerts cerebral benefits.
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Monitoring exercise-induced muscle damage indicators and myoelectric activity during two weeks of knee extensor exercise training in young and old men.
Heckel, Z, Atlasz, T, Tékus, É, Kőszegi, T, Laczkó, J, Váczi, M
PloS one. 2019;(11):e0224866
Abstract
This study considered the effects of repeated bouts of short-term resistive exercise in old (age: 64.5±5.5 years; n = 10) and young men (age: 25.1±4.9 years; n = 10) who performed six knee extension exercise bouts over two weeks using various markers of exercise-induced muscle damage and electromyographic activity. We found that time-course changes in quadriceps isometric torque, creatine kinase activity, and muscle soreness in the two groups were similar. However, recovery in the acute torque deficit was mediated by more favourable electromyographic activity changes in the young group than in the older adults group. Muscle elastic energy storage and re-use assessed with dynamometry was selectively improved in the young group by the end of the protocol. Serum myoglobin concentration increased selectively in old group, and remained elevated with further bouts, suggesting higher sarcolemma vulnerability and less effective metabolic adaptation in the older adults, which, however, did not affect muscle contractility.
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Trajectory of body mass and skeletal muscle indices and disease progression in metastatic colorectal cancer patients.
Kurk, SA, Stellato, RK, Peeters, PHM, Dorresteijn, B, Jourdan, M, Oskam, MJ, Punt, CJA, Koopman, M, May, AM
The American journal of clinical nutrition. 2019;(6):1395-1403
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BACKGROUND Knowledge of the evolution of BMI and skeletal muscle index (SMI) measurements during advanced cancer and their relationships with disease progression (PD) is relevant to improve the timing of interventions that may improve cachexia-associated outcomes. OBJECTIVES We investigated BMI and SMI trajectories and their associations with PD in metastatic colorectal cancer (mCRC) patients during consecutive palliative systemic regimens. METHODS In a secondary analysis of the primary CAIRO3 trial, we included 533 mCRC patients with BMI measurements repeated every 3 wk and 95 randomly selected patients with SMI measurements repeated every 9 wk. We studied 2 periods: p1, during first-line maintenance capecitabine + bevacizumab or observation until the first progression of disease (PD1); and p2, during capecitabine + oxaliplatin + bevacizumab or another reintroduction treatment from PD1 until the second progression of disease (PD2). BMI and SMI trajectories were modeled separately throughout both periods, and joint longitudinal-survival modeling was used to investigate the relationships between slopes in BMI and SMI with PD at 9 and 3 wk pre-PD. A multivariate longitudinal joint model was used to investigate the association between the BMI trajectory and PD at time of PD, independent of SMI. RESULTS During p1, the slopes in BMI and SMI were associated with early PD1 [HRs for 9-wk BMI: 1.54 (95% CI: 1.33, 1.76); 9-wk SMI: 1.38 (95% CI: 0.87, 1.89), NS; 3-wk BMI: 1.74 (95% CI: 1.48, 1.99); 3-wk SMI: 2.65 (95% CI: 1.97, 3.32)]. During p2, only the slope in SMI was related to PD2 [9-wk BMI: 1.09 (95%: CI: 0.73, 1.45), NS; 9-wk SMI: 1.64 (95% CI: 1.25, 2.04); 3-wk BMI: 1.17 (95% CI: 0.77, 1.57); 3-wk SMI: 1.11 (95% CI: 0.70, 1.53)]. In models mutually adjusting for BMI and SMI, SMI was associated with PD in p1 [p1 ( n = 95), HR BMI 1.32 (95% CI: 0.74, 2.39), NS; p1, HR SMI 1.50 (95% CI: 1.04, 2.14); p2 ( n = 50), BMI: 0.98 (95% CI: 0.55, 1.75), NS; p2, HR SMI 1.11 (95% CI: 0.61, 2.05), NS]. CONCLUSIONS In mCRC patients during palliative systemic treatment, SMI losses, irrespective of BMI losses, may be a marker for the early initiation of cachexia interventions.