Search

Exercise training is recommended for pulmonary hypertension (PH). Post hoc analysis of the PH and Home-Based (PHAHB) trial stratified patients into two groups based on median diffusing capacity of the lungs for carbon monoxide (DLCO). Patients with higher DLCO had a greater improvement in physical activity performance in response to exercise training, compared to those with lower DLCO. DLCO may be an important consideration in prescribing exercise in PH., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: Pulmonary hypertension (PH) is a heterogeneous condition, associated with a high symptom burden and a substantial loss of exercise capacity. Despite prior safety concerns regarding physical exertion, exercise training as a supportive therapy is now recommended for PH patients. Currently, most programmes are hospital-based, which limits accessibility. There is a need to provide alternative approaches for physical activity engagement for PH patients. The aim of this research was to develop, implement and evaluate the safety, feasibility and effectiveness of home-based physical activity intervention for PH., Methods: An entirely remotely delivered home-based physical activity intervention underpinned by behaviour change theory and informed by end-users, was assessed using a single-arm feasibility study design. Participants (n=19; 80% female) with a mean±sd age of 49.9±15.9 years with a diagnosis of PH undertook a 10-week, home-based physical activity intervention with induction training, support materials, telecommunication support, health coaching, exercise training and assessments, all remotely delivered. Training involved respiratory training along with a combination of aerobic and resistance exercises., Results: The intervention was deemed safe as no adverse events were reported. A high level of feasibility was demonstrated as the protocol was implemented as intended, sustained a high level of engagement and adherence and was well accepted by participants in terms of enjoyment and utility. There was a significant improvement in functional capacity, physical activity, exercise self-efficacy and quality of life, between baseline and post-training., Conclusion: The study demonstrates that an entirely remotely delivered home-based physical activity programme is safe, feasible and effective in improving functional capacity, physical activity and quality of life in PH patients., Competing Interests: Conflict of interest: B. Kehoe's institution has received grant funding for the submitted research from Actelion Pharmaceuticals. B. Kehoe has received grant funding from the National Cancer Control Programme and Irish Research Council, outside the work submitted. Conflict of interest: S. Gaine's institution has received grant funding for the submitted research from Actelion Pharmaceuticals. S. Gaine has received honoraria and speaker's fees from MSD and Janssen Pharmaceuticals, outside the submitted work; received travel support from MSD and Janssen Pharmaceuticals, outside the submitted work; participated in a data safety monitoring board for United Therapeutics and Janssen Pharmaceuticals; and has received consulting fees from or Altavant, Gossamer Bio, Janssen and MSD outside the submitted work. Conflict of interest: B. McCullagh has received honoraria, speaker's fees and travel support from Janssen Pharmaceuticals, outside the submitted work. Conflict of interest: N.M. Moyna's institution has received grant funding for the submitted research from Actelion Pharmaceuticals. N.M. Moyna has received grants from Enterprise Ireland and Health Service Executive, outside the submitted work; and received consulting fees from Irish Health Life, outside of the submitted work. Conflict of interest: All other authors have nothing to disclose., (Copyright ©The authors 2024.)

Objective: Physical activity (PA) is an established adjunct therapy for pulmonary hypertension (PH) patients to mitigate PH symptoms and improve quality of life. However, PA engagement within this population remains low. This study investigated PH patients' knowledge of PA, recalled advice, exercise preferences and PA support needs., Methods: Semi-structured interviews were conducted with 19 adults (mean age 50 years; SD ±12 years) diagnosed with PH, living in Ireland. Interview scripts were digitally recorded and transcribed verbatim. Thematic analysis was used to analyse the data., Results: Four key themes were identified: Lack of PA knowledge; exercise setting preference; accountability and monitoring; and clinician delivered PA information and guidance., Conclusion: This study found that PH clinicians provide suboptimal PA advice, yet patients desired clinician-delivered PA guidance. Home-based exercise was preferred with monitoring and external accountability deemed as important to facilitate sustained engagement., Practice Implications: PH clinicians are well positioned to play a critical role in assisting and empowering PH patients to engage in PA. Providing training and education to PH clinicians regarding exercise prescription may be beneficial. Further research is needed to evaluate the feasibility and efficacy of home-based exercise interventions to improve quality of life and physical activity in PH., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 McCormack et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ground based research modalities of microgravity have been proposed as innovative methods to investigate the aetiology of chronic age-related conditions such as cardiovascular disease. Dry Immersion (DI), has been effectively used to interrogate the sequelae of physical inactivity (PI) and microgravity on multiple physiological systems. Herein we look at the causa et effectus of 3-day DI on platelet phenotype, and correlate with both miRomic and circulating biomarker expression. The miRomic profile of platelets is reflective of phenotype, which itself is sensitive and malleable to the exposome, undergoing responsive transitions in order to fulfil platelets role in thrombosis and haemostasis. Heterogeneous platelet subpopulations circulate at any given time, with varying degrees of sensitivity to activation. Employing a DI model, we investigate the effect of acute PI on platelet function in 12 healthy males. 3-day DI resulted in a significant increase in platelet count, plateletcrit, platelet adhesion, aggregation, and a modest elevation of platelet reactivity index (PRI). We identified 15 protein biomarkers and 22 miRNA whose expression levels were altered after DI. A 3-day DI model of microgravity/physical inactivity induced a prothrombotic platelet phenotype with an unique platelet miRNA signature, increased platelet count and plateletcrit. This correlated with a unique circulating protein biomarker signature. Taken together, these findings highlight platelets as sensitive adaptive sentinels and functional biomarkers of epigenetic drift within the cardiovascular compartment., (© 2021. The Author(s).)

Pulmonary hypertension is a progressive cardiorespiratory disease that is characterized by considerable morbidity and mortality. While physical activity can improve symptoms and quality of life, engagement in this population is suboptimal. The aim of this study was to explore attitudes towards exercise and the dimensions that influence physical activity participation in individuals with pulmonary hypertension. Virtual, semi-structured interviews were conducted with individuals, with a formal diagnosis of pulmonary hypertension. Participants were recruited through the Pulmonary Hypertension Association of Ireland. Interviews were transcribed and analysed using thematic analysis. Nineteen patients were interviewed (n = 19). There was a female preponderance (n = 13) and the mean age was 50 ± 12 years. Three themes were identified and included fear, perceived value of exercise and environmental factors. Fear was the primary theme and included three sub-themes of fear of (i) over-exertion, (ii) physical damage and (iii) breathlessness. The perceived value of exercise encompassed two distinct sub-themes of perceived (i) exercise importance and (ii) benefits of exercise. Environmental factors included the terrain, weather conditions and location. Fear of overexertion, harm and dyspnoea strongly influenced attitudes to and engagement in physical activity. This study revealed heterogenous patient perspectives regarding the importance of physical activity and exercise. Future interventions that mitigate fear and promote the value of physical activity for individuals with pulmonary hypertension may have considerable benefits in promoting physical activity engagement. Such interventions require multidisciplinary involvement, including specialised pulmonary hypertension clinicians and exercise and behaviour change specialists., (© The Author(s) 2021.)

Background: Physical activity (PA) is a well-documented and accepted adjunct therapy for the maintenance and improvement of long-term health in cystic fibrosis (CF). Although the benefits of PA for CF populations are well-established, adherence to PA programmes within this population remains low. This study aimed to investigate the factors that influence engagement in physical activity, and to explore exercise preferences, among adults with cystic fibrosis (CF)., Methods: Semi-structured telephone interviews were conducted. Participants were twenty-one adults (mean age 35 years, SD ± 8) with an established diagnosis of CF, living in Ireland. Interview scripts were digitally recorded and transcribed verbatim. Thematic analysis was used to analyse the data., Results: Four main themes emerged: barriers, motives, value of exercise-related outcomes, and exercise preferences. The main barriers included: low energy levels, time, the weather, and exercise-related confidence. Enjoyment and perceived competence underpinned autonomous motivation. Participants who self-identified as being regularly active valued personally identified exercise-related outcomes such as, accomplishment and affect regulation. Participants indicated a preference for home-based physical activity programs compared to gym- or facility-based programs., Conclusion: Interventions aimed at promoting physical activity among adults with CF should involve programs that foster autonomous motivation, enjoyable activities, personally identified outcomes, competence and that can be conducted from the home environment., Clinical Implications: To increase physical activity participation among adults with CF, interventions that can be conducted from the home environment, that pay attention to the patients' personally-valued exercise outcomes may be required.

Background/objective: Measures of oxygen uptake efficiency (OUE) have been used to evaluate cardiorespiratory fitness (CRF) in adolescents unable to perform maximal exercise. The oxygen uptake efficiency slope (OUES) and oxygen uptake efficiency plateau (OUEP) have been proposed as surrogates for maximal oxygen consumption (V̇O 2max ). We assessed the validity of the OUES and OUEP as predictors of V̇O 2max in healthy male adolescents., Methods: Sixty-three healthy male adolescents aged 15.40 ± 0.34 years underwent an incremental treadmill test to determine V̇O 2max , OUES and OUEP. OUE throughout the test was assessed by dividing each V̇O 2 value by the corresponding minute ventilation (V̇ E ) value. OUEP was determined as the 90 s average highest consecutive values for OUE. OUES was determined using data up to the ventilatory threshold (VT) by calculating the slope of the linear relation between V̇O 2 and the logarithm of V̇ E ., Results: Limits of agreement for V̇O 2max predicted by OUES (±13.3 mL kg -1. min -1 ) and OUEP (±16.7 mL kg -1. min -1 ) relative to V̇O 2max were wide and a magnitude bias was found for OUES and OUEP as predictors of V̇O 2max (p < 0.001)., Conclusion: The OUES and OUEP do not accurately predict V̇O 2max in male adolescents and should not replace V̇O 2max when assessing CRF in this population., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2020 The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

Background: Physical activity (PA) is a well-established therapeutic modality for the maintenance and improvement of long-term health in cystic fibrosis (CF). Healthcare professionals (HCP) are considered credible and well-placed messengers for the delivery of PA advice. Limited research exists investigating the extent of PA prescription within CF care. This study aimed to identify Irish HCP i) knowledge and practice of, and ii) motivators and barriers to PA prescription, and iii) proposed strategies to optimize PA promotion and prescription in CF populations., Methods: HCP from six designated CF centres in Ireland and members of the national physiotherapy CF clinical interest group were invited to participate. Following an expression of interest, each HCP (n = 81) received an email containing the plain language statement and link to the online survey. 48 HCP (physiotherapists n = 24, other n = 24) completed the 30-item investigator-developed survey, which included multiple choice single answer, matrix style and open-ended questions., Results: Most HCP (81%) acknowledged that discussing PA with CF patients was part of their professional role. Almost all physiotherapists (95%) reported having sufficient knowledge regarding PA prescription, compared to 17% of other HCP. All physiotherapists reported discussing PA at every patient interaction, with 81% employing the current consensus guidelines, compared to 33 and 5% of other HCP, respectively. Among the most common barriers reported by HCP to recommending PA to their CF patients were; lack of motivation and compliance among patients to adhere to PA advice, limited availability of PA programmes to refer their patients to, limited time with patients during clinic visits and a lack of knowledge regarding PA prescription for CF care. Three-quarters of HCP reported a need to improve PA services for CF patients in Ireland., Conclusion: As people with CF are living longer, it is imperative that HCP are expanding their scope of practice to include discussions around PA at every patient visit. Formal educational opportunities in the form of continuing professional development programmes are warranted for CF HCP to optimize long-term patient management and outcomes. There is also a need to develop patient-centered and evidence-based PA programmes underpinned by theories of behaviour change to enhance motivation and compliance among CF patients.

Background: Exercise training provides benefits for individuals with cystic fibrosis; however, the optimal program is unclear. High-intensity interval training is safe and effective for improving 'functional capacity' in these individuals with peak rate of O 2 uptake typically referenced. The ability to adjust submaximal rate of oxygen uptake (V̇O 2 kinetics) might be more important for everyday function because maximal efforts are usually not undertaken. Moreover, the ability of high-intensity training to accelerate V̇O 2 kinetics for individuals with cystic fibrosis could be enhanced with O 2 supplementation during training., Methods: Nine individuals with cystic fibrosis completed incremental cycling to limit of tolerance followed by 8 weeks of high-intensity interval cycling (2 sessions per week x ~ 45 min per session) either with ( n  = 5; O2+) or without (AMB) oxygen supplementation (100%). Each session involved work intervals at 70% of peak work rate followed by 60 s of recovery at 35%. For progression, duration of work intervals was increased according to participant tolerance., Results: Both groups experienced a significant increase in work-interval duration over the course of the intervention (O2+, 1736 ± 141 v . 700 ± 154 s; AMB, 1463 ± 598 v . 953 ± 253 s; P  = 0.000); however, the increase experienced by O2+ was greater ( P  = 0.027). During low-intensity constant-work-rate cycling, the V̇O 2 mean response time was shortened post compared to pre training (O2+, 34 ± 11 v . 44 ± 9 s; AMB, 39 ± 14 v . 45 ± 17 s; P  = 0.000) while during high-intensity constant-work-rate cycling, time to exhaustion was increased (O2+, 1628 ± 163 v . 705 ± 133 s; AMB, 1073 ± 633 v . 690 ± 348 s; P  = 0.002) and blood [lactate] response was decreased (O2+, 4.5 ± 0.9 v . 6.3 ± 1.4 mmol . L - 1 ; AMB, 4.5 ± 0.6 v . 5.2 ± 1.4 mmol . L - 1 ; P  = 0.003). These positive adaptations were similar regardless of gas inspiration during training., Conclusion: Eight weeks of high-intensity interval training for patients with cystic fibrosis accelerated V̇O 2 kinetics and increased time to exhaustion. This provides some evidence that these patients may benefit from this type of exercise., Trial Registration: This study was retrospectively registered in the ISRTCN registry on 22/06/2019 (#ISRCTN13864650)., Competing Interests: Competing interestsFJD is editor of the Exercise Physiology section of BMC Sports, Science, Medicine and Rehabilitation., (© The Author(s). 2020.)

Glucocorticoid receptor (NR3C1) polymorphisms associate with obesity, muscle strength, and cortisol sensitivity. We examined associations among four NR3C1 polymorphisms and the muscle response to resistance training (RT). European-American adults (n = 602, 23.8±0.4yr) completed a 12 week unilateral arm RT program. Maximum voluntary contraction (MVC) assessed isometric strength (kg) and MRI assessed biceps size (cm2) pre- and post-resistance training. Subjects were genotyped for NR3C1 -2722G>A, -1887G>A, -1017T>C, and +363A>G. Men carrying the -2722G allele gained less relative MVC (17.3±1.2vs33.5±6.1%) (p = 0.010) than AA homozygotes; men with -1887GG gained greater relative MVC than A allele carriers (19.6±1.4vs13.2±2.3%) (p = 0.016). Women carrying the -1017T allele gained greater relative size (18.7±0.5vs16.1±0.9%) (p = 0.016) than CC homozygotes. We found sex-specific NR3C1 associations with the muscle strength and size response to RT. Future studies should investigate whether these associations are partially explained by cortisol's actions in muscle tissue as they interact with sex differences in cortisol production.

Background: Meta-analysis of genome-wide association studies identified obesity-related genetic variants. Due to the pleiotropic effects of related phenotypes, we tested six of these obesity-related genetic variants for their association with physical activity: fat mass and obesity-associated ( FTO )(rs9939609)T>A, potassium channel tetramerization domain containing ( KCTD15 ) (rs11084753)G>A, melanocortin receptor4 ( MC4R )(rs17782313)T>C, neuronal growth regulator 1 ( NEGR1 )(rs2815752)A>G, SH2B adapter protein 1 ( SH2B1 )(rs7498665)A>G, and transmembrane protein18 ( TMEM18 )(rs6548238)C>T., Method: European-American women ( n  = 263) and men ( n  = 229) (23.5 ± 0.3 years, 24.6 ± 0.2 kg/m 2 ) were genotyped and completed the Paffenbarger physical activity Questionnaire. Physical activity volume in metabolic energy equivalents [MET]-hour/week was derived from the summed time spent (hour/week) times the given MET value for vigorous, moderate, and light intensity physical activity, and sitting and sleeping, respectively. Multivariable adjusted [(age, sex, and body mass index (BMI)] linear regression tested associations among genotype (dominant/recessive model) and the log of physical activity volume., Result: MC4R (rs17782313)T>C explained 1.1 % ( p  = 0.02), TMEM18 (rs6548238)C>T 1.2 % ( p  = 0.01), and SH2B1 (rs7498665)A>G 0.6 % ( p  = 0.08) of the variability in physical activity volume. Subjects with the MC4R C allele spent 3.5 % less MET-hour/week than those with the TT genotype ( p  = 0.02). Subjects with the TMEM18 T allele spent 4.1 % less MET-hour/week than those with the CC genotype ( p  = 0.01). Finally, subjects with the SH2B1 GG genotype spent 3.6 % less MET-hour/week than A allele carriers ( p  = 0.08)., Conclusion: Our findings suggest a shared genetic influence among some obesity-related gene loci and physical activity phenotypes that should be explored further. Physical activity volume differences by genotype have public health importance equating to 11-13 lb weight difference annually.

Genome-wide association studies have identified thousands of variants that are associated with numerous phenotypes. One such variant, rs13266634, a nonsynonymous single nucleotide polymorphism in the solute carrier family 30 (zinc transporter) member eight gene, is associated with a 53% increase in the risk of developing type 2 diabetes (T2D). We hypothesized that individuals with the protective allele against T2D would show a positive response to short-term and long-term resistance exercise. Two cohorts of young adults-the Eccentric Muscle Damage (EMD; n = 156) cohort and the Functional Single Nucleotide Polymorphisms Associated with Muscle Size and Strength Study (FAMuSS; n = 874)-were tested for association of the rs13266634 variant with measures of skeletal muscle response to resistance exercise. Our results were sexually dimorphic in both cohorts. Men in the EMD study with two copies of the protective allele showed less post-exercise bout strength loss, less soreness, and lower creatine kinase values. In addition, men in the FAMuSS, homozygous for the protective allele, showed higher pre-exercise strength and larger arm skeletal muscle volume, but did not show a significant difference in skeletal muscle hypertrophy or strength with resistance training.

Purpose: An osteopontin (OPN; SPP1) gene promoter polymorphism modifies disease severity in Duchenne muscular dystrophy, and we hypothesized that it might also modify muscle phenotypes in healthy volunteers., Methods: Gene association studies were carried out for OPN (rs28357094) in the FAMuSS cohort (n = 752; mean ± SD age = 23.7 ± 5.7 yr). The phenotypes studied included muscle size (MRI), strength, and response to supervised resistance training. We also studied 147 young adults that had carried out a bout of eccentric elbow exercise (age = 24.0 ± 5.2 yr). Phenotypes analyzed included strength, soreness, and serum muscle enzymes., Results: In the FAMuSS cohort, the G allele was associated with 17% increase in baseline upper arm muscle volume only in women (F = 26.32; P = 5.32 × 10), explaining 5% of population variance. In the eccentric damage cohort, weak associations of the G allele were seen in women with both baseline myoglobin and elevated creatine kinase. The sexually dimorphic effects of OPN on muscle were also seen in OPN-null mice. Five of seven muscle groups examined showed smaller size in OPN-null female mice, whereas two were smaller in male mice. The query of OPN gene transcription after experimental muscle damage in mice showed rapid induction within 12 h (100-fold increase from baseline), followed by sustained high-level expression through 16 d of regeneration before falling to back to baseline., Conclusion: OPN is a sexually dimorphic modifier of muscle size in normal humans and mice and responds to muscle damage. The OPN gene is known to be estrogen responsive, and this may explain the female-specific genotype effects in adult volunteers.

Purpose: We investigated the influence of Leptin (LEP) and leptin receptor (LEPR) SNPs on habitual physical activity (PA) and body composition response to a unilateral, upper body resistance training (RT) program., Methods: European-derived American volunteers (men=111, women=131, 23.4 ± 5.4 yr, 24.4 ± 4.6 kg·m(-2)) were genotyped for LEP 19 G>A (rs2167270), and LEPR 326 A>G (rs1137100), 668 A>G (rs1137101), 3057 G>A (rs1805096), and 1968 G>C (rs8179183). They completed the Paffenbarger PA Questionnaire. Arm muscle and subcutaneous fat volumes were measured before and after 12 wk of supervised RT with MRI. Multivariate and repeated measures ANCOVA tested differences among phenotypes by genotype and gender with age and body mass index as covariates., Results: Adults with the LEP 19 GG genotype reported more kcal/wk in vigorous intensity PA (1273.3 ± 176.8, p=0.017) and sports/recreation (1922.8 ± 226.0, p<0.04) than A allele carriers (718.0 ± 147.2, 1328.6 ± 188.2, respectively). Those with the LEP 19 GG genotype spent more h/wk in light intensity PA (39.7 ± 1.6) than A allele carriers (35.0 ± 1.4, p=0.03). In response to RT, adults with the LEPR 668 G allele gained greater arm muscle volume (67,687.05 ± 3186.7 vs. 52,321.87 ± 5125.05 mm(3), p=0.01) and subcutaneous fat volume (10,599.89 ± 3683.57 vs. -5224.73 ± 5923.98 mm(3), p=0.02) than adults with the LEPR 668 AA genotype, respectively., Conclusion: LEP19 G>A and LEPR 668 A>G associated with habitual PA and the body composition response to RT. These LEP and LEPR SNPs are located in coding exons likely influencing LEP and LEPR function. Further investigation is needed to confirm our findings and establish mechanisms for LEP and LEPR genotype and PA and body composition associations we observed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Many of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects., Methods: Using a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL)., Results: The intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70-120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43-55 nm (medium) particle range. VLDL-TG in smaller particles (29-43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state., Conclusions: These findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity.

Background: Quadriceps femoris muscle (QFM) weakness is a feature of knee osteoarthritis (OA) and exercise programs that strengthen this muscle group can improve function, disability and pain. Traditional supervised resistance exercise is however resource intensive and dependent on good adherence which can be challenging to achieve in patients with significant knee OA. Because of the limitations of traditional exercise programs, interest has been shown in the use of neuromuscular electrical stimulation (NMES) to strengthen the QFM. We conducted a single-blind, prospective randomized controlled study to compare the effects of home-based resistance training (RT) and NMES on patients with moderate to severe knee OA., Methods: 41 patients aged 55 to 75 years were randomised to 6 week programs of RT, NMES or a control group receiving standard care. The primary outcome was functional capacity measured using a walk test, stair climb test and chair rise test. Additional outcomes were self-reported disability, quadriceps strength and cross-sectional area. Outcomes were assessed pre- and post-intervention and at 6 weeks post-intervention (weeks 1, 8 and 14 respectively)., Results: There were similar, significant improvements in functional capacity for the RT and NMES groups at week 8 compared to week 1 (p ≤ 0.001) and compared to the control group (p < 0.005), and the improvements were maintained at week 14 (p ≤ 0.001). Cross sectional area of the QFM increased in both training groups (NMES: +5.4%; RT: +4.3%; p = 0.404). Adherence was 91% and 83% in the NMES and RT groups respectively (p = 0.324)., Conclusions: Home-based NMES is an acceptable alternative to exercise therapy in the management of knee OA, producing similar improvements in functional capacity., Trial Registration: Current Controlled Trials ISRCTN85231954.

Background: Emerging data have revealed a negative association between adiposity and muscle quality (MQ). There is a lack of research to examine this interaction among young, healthy individuals, and to evaluate the contribution of adiposity to adaptation after resistance exercise (RE)., Objective: The purpose of this investigation was to examine the influence of subcutaneous adipose tissue (SAT) on muscle function among non-obese individuals before and after RE., Design: Analyses included 634 non-obese (body mass index <30 kg m(-2)) subjects (253 males, 381 females; age=23.3 ± 5.2 years). SAT and muscle mass (magnetic resonance imaging-derived SAT and biceps muscle volume), isometric and dynamic biceps strength, and MQ (strength/muscle volume), were analyzed at baseline and after 12 weeks of unilateral RE., Results: At baseline, SAT was independently associated with lower MQ for males (β=-0.55; P<0.01) and females (β=-0.45; P<0.01), controlling for body mass and age. Adaptation to RE revealed a significant negative association between SAT and changes for strength capacity (β=-0.13; p=0.03) and MQ (β=-0.14; P<0.01) among males. No attenuation was identified among females. Post-intervention SAT remained a negative predictor of MQ for males and females (β=-0.47; P<0.01)., Conclusions: The findings reveal that SAT is a negative predictor of MQ among non-obese, healthy adults, and that after 12 weeks of progressive RE this association was not ameliorated. Data suggest that SAT exerts a weak, negative influence on the adaptive response to strength and MQ among males.

Genome-wide association studies (GWASs) have identified polymorphic loci associated with coronary artery disease (CAD) risk factors (i.e. serum lipids) in adult populations (42-69 y). We hypothesized that younger populations would show a greater relative genetic component due to fewer confounding variables. We examined the influence of 20 GWAS loci associated with serum lipids and insulin metabolism, in a university student cohort (n = 548; mean age = 24 y), and replicated statistically associated results in a second study cohort of primary school students (n = 810, mean age = 11.5 y). Nineteen loci showed no relationship with studied risk factors in young adults. However, the ancestral allele of the rs646776 (SORT1) locus was strongly associated with increased LDL (C) in young adults [TT: 97.6 ± 1.0 mg/dL (n = 345) versus CT/CC: 87.3 ± 1.0 mg/dL (n = 203); p = 3 × 10(x6)] and children [TT: 94.0 ± 1.3 mg/dL (n = 551) versus CT/CC: 84.7 ± 1.4 mg/dL (n = 259); p = 4 × 10(x6)]. This locus is responsible for 3.6% of population variance in young adults and 2.5% of population variance in children. The effect size of the SORT1 locus is considerably higher in young populations (2.5-4.1%) compared with older subjects (1%).

Hepatic lipase (HL) and lipoprotein lipase (LPL) activities (HLA, LPLA) modify lipoproteins and facilitate their binding to hepatic receptors. Apolipoprotein E (APOE) physically interacts with the lipases, and the three common haplotypes of the APOE gene (ε2, ε3, and ε4) yield protein isoforms (E2, E3, and E4, respectively) that are functionally different. Lipase activities themselves differ by sex and exercise training status. The interaction of APOE genotype, exercise training, and sex effects on lipase activities has not been studied. We measured postheparin plasma lipase activities in normolipidemic men and women with the three most common APOE genotypes, which are the haplotype combinations ε2/ε3 (n = 53 ), ε3/ε3 (n = 62), and ε4/ε3 (n = 52), enrolled in 6 mo of aerobic exercise training. These haplotype combinations comprise an estimated 11.6, 62.3, and 21.3% of the population, respectively. Baseline HLA was 35% lower in women than in men (P < 0.0001). In men but not women, HLA was higher in ε2/ε3 group compared with ε4/ε3 (P = 0.01) and ε3/ε3 (P = 0.05). Neither sex nor APOE genotype affected baseline LPLA. Training decreased HLA by 5.2% (P = 0.018) with no APOE effect. The apparent increase in LPLA following exercise was significant and APOE dependent only when corrected for baseline insulin (P < 0.05). Exercise decreased LPLA by 0.8 μmol free fatty acid (FFA)·ml⁻¹·h⁻¹ (-6%) in ε3/ε3 compared with the combined increases of 6.6% in ε2/ε3 and 12% in ε4/ε3 (P = 0.018 vs. ε3/ε3). However, these differences were statistically significant only after correcting for baseline insulin. We conclude that common APOE genotypes interact with 1) sex to modulate HLA regardless of training status, with ε2/ε3 men demonstrating higher HLA than ε3/ε3 or ε4/ε3 men, and 2) aerobic training to modulate LPLA, regardless of sex, with ε3/ε3 subjects showing a significant decrease compared with an increase in ε2/ε3 and ε3/ε4 after controlling for baseline insulin.

Recently, a genome-wide association study (GWAS) that identified eight single-nucleotide polymorphisms (SNPs) associated with BMI highlighted a possible neuronal influence on the development of obesity. We hypothesized these SNPs would govern the response of BMI and subcutaneous fat to resistance training in young individuals (age = 24 years). We genotyped the eight GWAS-identified SNPs in the article by Willer et al. in a cohort (n = 796) that undertook a 12-week resistance-training program. Females with a copy of the rare allele (C) for rs17782313 (MC4R) had significantly higher BMIs (, Cc/ct: n = 174; 24.70 ± 0.33 kg/m², TT: n = 278; 23.41 ± 0.26 kg/m², P = 0.002), and the SNP explained 1.9% of overall variation in BMI. Males with a copy of the rare allele (T) for rs6548238 (TMEM18) had lower amounts of subcutaneous fat pretraining (CT/TT: n = 65; 156,534 ± 7,415 mm³, CC: n = 136; 177,825 ± 5,139 mm³, P = 0.019) and males with a copy of the rare allele (A) for rs9939609 (FTO) lost a significant amount of subcutaneous fat with exercise (, At/aa: n = 83; -798.35 ± 2,624.30 mm³, TT: n = 47; 9,435.23 ± 3,494.44 mm³, P = 0.021). Females with a copy of the G allele for a missense variant in the SH2B1 (rs7498665) was associated with less change of subcutaneous fat volume with exercise (, Ag/gg: n = 191; 9,813 ± 2,250 mm³ vs. AA: n = 126; 770 ± 2,772 mm³; P = 0.011). These data support the original finding that there is an association between measures of obesity and a variant near the MC4R gene and extends these results to a younger population and implicates FTO, TMEM18, and SH2B1 polymorphisms in subcutaneous fat regulation.

Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin,insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that makeup metabolic syndrome. We studied a 12-kb region including the first exon of the AKT1 gene for association with metabolic syndrome-related phenotypes in four study populations [FAMUSS cohort (n = 574; age 23.7 ± 5.7 years), Strong Heart Study (SHS) (n = 2,134; age 55.5 ± 7.9 years), Dynamics of Health, Aging and Body Composition (Health ABC) (n = 3,075; age 73.6 ± 2.9 years), and Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE)(n = 175; age 40–65 years)]. We identified a three SNP haplotype that we call H1, which represents the ancestral alleles eles at the three loci and H2, which represents the derived alleles at the three loci. In young adult European Americans (FAMUSS), H1 was associated with higher fasting glucose levels in females. In middle age Native Americans (SHS), H1 carriers showed higher fasting insulin and HOMA in males, and higher BMI in females. Inolder African-American and European American subjects(Health ABC) H1 carriers showed a higher incidence of metabolic syndrome. Homozygotes for the H1 haplotype showed about twice the risk of metabolic syndrome in both males and females (p < 0.001). In middle-aged European Americans with insulin resistance (STRRIDE) studied by intravenous glucose tolerance test (IVGTT), H1 carriers showed increased insulin resistance due to the Sg component (p = 0.021). The 12-kb haplotype is a risk factor for metabolic syndrome and insulin resistance that needs to be explored in further populations.

Baseline muscle size and muscle adaptation to exercise are traits with high variability across individuals. Recent research has implicated several chemokines and their receptors in the pathogenesis of many conditions that are influenced by inflammatory processes, including muscle damage and repair. One specific chemokine, chemokine (C-C motif) ligand 2 (CCL2), is expressed by macrophages and muscle satellite cells, increases expression dramatically following muscle damage, and increases expression further with repeated bouts of exercise, suggesting that CCL2 plays a key role in muscle adaptation. The present study hypothesizes that genetic variations in CCL2 and its receptor (CCR2) may help explain muscle trait variability. College-aged subjects [n = 874, Functional Single-Nucleotide Polymorphisms Associated With Muscle Size and Strength (FAMUSS) cohort] underwent a 12-wk supervised strength-training program for the upper arm muscles. Muscle size (via MR imaging) and elbow flexion strength (1 repetition maximum and isometric) measurements were taken before and after training. The study participants were then genotyped for 11 genetic variants in CCL2 and five variants in CCR2. Variants in the CCL2 and CCR2 genes show strong associations with several pretraining muscle strength traits, indicating that inflammatory genes in skeletal muscle contribute to the polygenic system that determines muscle phenotypes. These associations extend across both sexes, and several of these genetic variants have been shown to influence gene regulation.

Background: Supervised preoperative muscle strengthening programmes (prehabilitation) can improve recovery after total joint arthroplasty but are considered resource intensive. Neuromuscular electrical stimulation (NMES) has been shown to improve quadriceps femoris muscle (QFM) strength and clinical function in subjects with knee osteoarthritis (OA) however it has not been previously investigated as a prehabilitation modality., Methods: This pilot study assessed the compliance of a home-based, NMES prehabilitation programme in patients undergoing total knee arthroplasty (TKA). We evaluated its effect on preoperative and postoperative isometric quadriceps femoris muscle (QFM) strength, QFM cross-sectional area (CSA) and clinical function (subjective and objective). Seventeen subjects were recruited with 14 completing the study (NMES group n = 9; Control group n = 5)., Results: Overall compliance with the programme was excellent (99%). Preoperative QFM strength increased by 28% (p > 0.05) with associated gains in walk, stair-climb and chair-rise times (p < 0.05). Early postoperative strength loss (approximately 50%) was similar in both groups. Only the NMES group demonstrated significant strength (53.3%, p = 0.011) and functional recovery (p < 0.05) from 6 to 12 weeks post-TKA. QFM CSA decreased by 4% in the NMES group compared to a reduction of 12% in the control group (P > 0.05) at 12 weeks postoperatively compared to baseline. There were only limited associations found between objective and subjective functional outcome instruments., Conclusions: This pilot study has shown that preoperative NMES may improve recovery of quadriceps muscle strength and expedite a return to normal activities in patients undergoing TKA for OA. Recommendations for appropriate outcome instruments in future studies of prehabilitation in TKA have been provided.

Skeletal muscle contraction increases intracellular ATP turnover, calcium flux, and mechanical stress, initiating signal transduction pathways that modulate peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha)-dependent transcriptional programmes. The purpose of this study was to determine if the intensity of exercise regulates PGC-1alpha expression in human skeletal muscle, coincident with activation of signalling cascades known to regulate PGC-1alpha transcription. Eight sedentary males expended 400 kcal (1674 kj) during a single bout of cycle ergometer exercise on two separate occasions at either 40% (LO) or 80% (HI) of . Skeletal muscle biopsies from the m. vastus lateralis were taken at rest and at +0, +3 and +19 h after exercise. Energy expenditure during exercise was similar between trials, but the high intensity bout was shorter in duration (LO, 69.9 +/- 4.0 min; HI, 36.0 +/- 2.2 min, P < 0.05) and had a higher rate of glycogen utilization (P < 0.05). PGC-1alpha mRNA abundance increased in an intensity-dependent manner +3 h after exercise (LO, 3.8-fold; HI, 10.2-fold, P < 0.05). AMP-activated protein kinase (AMPK) (2.8-fold, P < 0.05) and calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylation (84%, P < 0.05) increased immediately after HI but not LO. p38 mitogen-activated protein kinase (MAPK) phosphorylation increased after both trials (2.0-fold, P < 0.05), but phosphorylation of the downstream transcription factor, activating transcription factor-2 (ATF-2), increased only after HI (2.4-fold, P < 0.05). Cyclic-AMP response element binding protein (CREB) phosphorylation was elevated at +3 h after both trials (80%, P < 0.05) and class IIa histone deacetylase (HDAC) phosphorylation increased only after HI (2.0-fold, P < 0.05). In conclusion, exercise intensity regulates PGC-1alpha mRNA abundance in human skeletal muscle in response to a single bout of exercise. This effect is mediated by differential activation of multiple signalling pathways, with ATF-2 and HDAC phosphorylation proposed as key intensity-dependent mediators.

Unlabelled: Participation in regular aerobic exercise has been shown to increase arterial size and that exercise-induced vascular remodeling may be regional rather than systemic. However, these issues have been minimally investigated concerning resistance training., Purposes: To determine whether 1) resistance training of the nondominant arm elicits an increase in diameter of the brachial artery and 2) unilateral training induces arterial remodeling in the contralateral arm., Methods: Twenty-four previously untrained participants, consisting of 18 females (aged 22.3 +/- 5.1 yr) and 6 males (aged 21.7 +/- 1.8 yr), participated in unilateral strength training of the biceps and triceps for 12 wk using their nondominant arm. Isotonic (one-repetition maximum, 1RM) and isometric (ISO) strength of the biceps were assessed before and after training on both arms. Brachial artery diameter and biceps muscle cross-sectional area (CSA) of both arms were also measured before and after training using magnetic resonance imaging (MRI)., Results: Brachial artery diameter increased 5.47% (P < 0.05) in the nondominant trained arm with no change observed in the dominant untrained arm. Biceps CSA increased 18.3% (P < 0.05) in the trained arm with no change (P > 0.05) in the untrained limb. Nondominant 1RM and ISO strength increased by 35.1% and 16.8%, respectively (P < 0.05 for both), although there were no significant changes (P > 0.05) in the contralateral arm. A modest correlation was found between the increases in CSA and in brachial artery diameter (r2 = 0.19, P = 0.039)., Conclusions: These results indicate that upper arm vascular remodeling, manifesting as increased brachial artery diameter, can result from resistance training and that these changes are localized to the trained limb and associated with increases in CSA.

The present study examined associations between the ciliary neurotrophic factor (CNTF) 1357 G --> A polymorphism and the muscle strength response to a unilateral, upper arm resistance-training (RT) program among healthy, young adults. Subjects were 754 Caucasian men (40%) and women (60%) who were genotyped and performed a training program of the nondominant (trained) arm with the dominant (untrained) arm as a comparison. Peak elbow flexor strength was measured with one repetition maximum, isometric strength with maximum voluntary contraction, and bicep cross-sectional area with MRI in the trained and untrained arms before and after training. Women with the CNTF GG genotype gained more absolute isometric strength, as measured by MVC (6.5 +/- 0.3 vs. 5.2 +/- 0.5 kg), than carriers of the CNTF A1357 allele in the trained arm pre- to posttraining (P < 0.05). No significant associations were seen in men. Women with the CNTF GG genotype gained more absolute dynamic (1.0 +/- 0.1 vs. 0.6 +/- 0.1 kg) and allometric (0.022 +/- 0.0 vs. 0.015 +/- 0.0 kg/kg(-0.67)) strength, as measured by 1 RM, than carriers of the CNTF A1357 allele in the untrained arm pre- to posttraining (P < 0.05). No significant associations were seen in men. No significant associations, as measured by cross-sectional area, were seen in men or women. The CNTF 1357 G --> A polymorphism explains only a small portion of the variability in the muscle strength response to training in women.

Purpose: We examined associations among myostatin (MSTN) 2379 A > G and 163 G > A and follistatin (FST) -5003 A > T and -833 G > T single nucleotide polymorphisms (SNP) on the muscle size and the strength response to resistance training (RT)., Methods: Subjects (n = 645, age = 24.1 +/- 0.2 yr, body mass index [BMI] = 24.2 +/- 0.2 kg x m(-2)) self-disclosed themselves as Caucasian (78.9%), African American (3.6%), Asian (8.4%), Hispanic (5.0%), or Other (4.2%). They were genotyped for MSTN 2379 A > G (n = 645), MSTN 163 G > A (n = 639), FST -5003 A > T (n = 580), and FST -833 G > T (n = 603). We assessed dynamic (one repetition maximum [1RM]) and isometric (maximum voluntary contraction [MVC]) muscle strength and size (cross-sectional area [CSA]) of the elbow flexors before and after 12 wk of unilateral upper-arm RT. Repeated-measures ANCOVA tested associations among genetic variants and muscle phenotypes with age and BMI as covariates., Results: Baseline MVC was greater among African Americans who were carriers of the MSTN G(2379) allele (AG/GG, n = 15) than the A2379A homozygotes (n = 8; 64.2 +/- 6.8 vs 49.8 +/- 8.7 kg). African Americans who were carriers of the FST T(-5003) allele (n = 12) had greater baseline 1RM (11.9 +/- 0.7 vs 8.8 +/- 0.5 kg) and CSA (24.4 +/- 1.3 vs 19.1 +/- 1.2 cm(2)) than African Americans with the A-5003A genotype (n = 14; P < 0.05). No MSTN or FST genotype and muscle phenotype associations were found among the other ethnic groups (P >or= 0.05)., Conclusion: MSTN 2379 A > G and FST -5003 A > T were associated with baseline muscle strength and size among African Americans only. These ethnic-specific associations are hypothesis generating and should be confirmed in a larger sample of African Americans.

Acute exercise, undertaken on the day before an oral fat tolerance test (OFTT), typically reduces postprandial triglycerides (TG) and increases high-density lipoprotein-cholesterol (HDL-C). However, the benefits of acute exercise may be overstated when studies do not account for compensatory changes in dietary intake. The objective of this study was to determine the influence of acute exercise, with and without carbohydrate (CHO) replacement, on postprandial lipid metabolism. Eight recreationally active young men underwent an OFTT on the morning after three experimental conditions: no exercise [control (Con)], prolonged exercise without CHO replacement (Ex-Def) and prolonged exercise with CHO replacement to restore CHO and energy balance (Ex-Bal). The exercise session in Ex-Def and Ex-Bal consisted of 90 min cycle ergometry at 70% peak oxygen uptake (Vo(2peak)) followed by 10 maximal 1-min sprints. CHO replacement was achieved using glucose solutions consumed at 0, 2, and 4 h postexercise. Muscle glycogen was 40 +/- 4% (P < 0.05) and 94 +/- 3% (P = 0.24) of Con values on the morning of the Ex-Def and Ex-Bal OFTT, respectively. Postprandial TG were 40 +/- 14% lower and postprandial HDL-C, free fatty acids, and 3-hydroxybutyrate were higher in Ex-Def compared with Con (P < 0.05). Most importantly, these exercise effects were not evident in Ex-Bal. Postprandial insulin and glucose and the homeostatic model assessment of insulin resistance (HOMA(IR)) were not significantly different across trials. There was no relation between the changes in postprandial TG and muscle glycogen across trials. In conclusion, the influence of acute exhaustive exercise on postprandial lipid metabolism is largely dependent on the associated CHO and energy deficit.

Background: A common SNP upstream of the INSIG2 gene, rs7566605 (g.-10,1025G>C, Chr2:118,552,255, NT&#95;022135.15), was reported to be associated with obesity (Body Mass Index, [BMI]) in a genome-wide association scan using the Framingham Heart Study but has not been reproduced in other cohorts. As BMI is a relatively insensitive measure of adiposity that is subject to many confounding variables, we sought to determine the relationship between the INSIG2 SNP and subcutaneous fat volumes measured by MRI in a young adult population., Methods: We genotyped the INSIG2 SNP rs7566605 in college-aged population enrolled in a controlled resistance-training program, (the Functional Polymorphism Associated with Human Muscle Size and Strength, FAMuSS cohort, n = 752 volunteers 18-40 yrs). In this longitudinal study, we examined the effect of the INSIG2 polymorphism on subcutaneous fat and muscle volumes of the upper arm measured by magnetic resonance imaging (MRI) before and after 12 wks of resistance training. Gene/phenotype associations were tested using an analysis of covariance model with age and weight as covariates. Further, the % variation in each phenotype attributable to genotype was determined using hierarchical models and tested with a likelihood ratio test., Results: Women with a copy of the C allele had higher levels of baseline subcutaneous fat (GG: n = 139; 243473 +/- 5713 mm3 vs. GC/CC: n = 181; 268521 +/- 5003 mm3; p = 0.0011); but men did not show any such association. Men homozygous for the G ancestral allele showed a loss of subcutaneous fat, while those with one or two copies of the C allele gained a greater percentage of subcutaneous fat with resistance training (GG: n = 103; 1.02% +/- 1.74% vs. GC/CC: n = 93; 6.39% +/- 1.82%; p = 0.035)., Conclusion: Our results show that the INSIG2 rs7566605 polymorphism underlies variation in subcutaneous adiposity in young adult women and suppresses the positive effects of resistance training on men. This supports and extends the original finding that there is an association between measures of obesity and INSIG2 rs7566605 and further implicates this polymorphism in fat regulation.

The aims of this study were to examine associations between two SNPs in the human IL-15 gene and three SNPs in the IL-15Ralpha gene with predictors of metabolic syndrome and phenotypes in muscle, strength, and bone at baseline and in response to resistance training (RT). Subjects were Caucasians who had not performed RT in the previous year and consisted of a strength cohort (n=748), volumetric cohort (n=722), and serum cohort (n=544). Subjects completed 12 weeks of unilateral RT of the non-dominant arm, using their dominant arm as an untrained control. ANCOVA analyses revealed gender-specific associations with: (1) IL-15 SNP (rs1589241) and cholesterol (p=0.04), LDL (p=0.02), the homeostasis model assessment (HOMA; p=0.03), and BMI (p=0.002); (2) IL-15 SNP (rs1057972) and the pre- to post-training absolute difference in 1RM strength (p=0.02), BMI (p=0.008), and fasting glucose (p=0.03); (3) IL-15Ralpha SNP (rs2296135) and baseline total bone volume (p=0.04) and the pre- to post-training absolute difference in isometric strength (p=0.01); and 4) IL-15Ralpha SNP (rs2228059) and serum triglycerides (p=0.04), baseline whole muscle volume (p=0.04), baseline cortical bone volume (p=0.04), and baseline muscle quality (p=0.04). All associations were consistent in showing a potential involvement of the IL-15 pathway with muscle and bone phenotypes and predictors of metabolic syndrome.

Background: Walking and cycling to school provide a convenient opportunity to incorporate physical activity into an adolescent's daily routine. School proximity to residential homes has been identified as an important determinant of active commuting among children. The purpose of this study is to identify if distance is a barrier to active commuting among adolescents, and if there is a criterion distance above which adolescents choose not to walk or cycle., Methods: Data was collected in 2003-05 from a cross-sectional cohort of 15-17 yr old adolescents in 61 post primary schools in Ireland. Participants self-reported distance, mode of transport to school and barriers to active commuting. Trained researchers took physical measurements of height and weight. The relation between mode of transport, gender and population density was examined. Distance was entered into a bivariate logistic regression model to predict mode choice, controlling for gender, population density socio-economic status and school clusters., Results: Of the 4013 adolescents who participated (48.1% female, mean age 16.02 +/- 0.661), one third walked or cycled to school. A higher proportion of males than females commuted actively (41.0 vs. 33.8%, chi2 (1) = 22.21, p < 0.001, r = -0.074). Adolescents living in more densely populated areas had greater odds of active commuting than those in the most sparsely populated areas (chi2 (df = 3) = 839.64, p < 0.001). In each density category, active commuters travelled shorter distances to school. After controlling for gender and population density, a 1-mile increase in distance decreased the odds of active commuting by 71% (chi2 (df = 1) = 2591.86, p < 0.001). The majority of walkers lived within 1.5 miles and cyclists within 2.5 miles. Over 90% of adolescents who perceived distance as a barrier to active commuting lived further than 2.5 miles from school., Conclusion: Distance is an important perceived barrier to active commuting and a predictor of mode choice among adolescents. Distances within 2.5 miles are achievable for adolescent walkers and cyclists. Alternative strategies for increasing physical activity are required for individuals living outside of this criterion.

Background: Of the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components (typically 50-80% of population variation). Studies defining genetic predispositions have typically focused on older populations with metabolic syndrome and/or type 2 diabetes. We hypothesized that the study of younger populations would mitigate many confounding variables, and allow us to better define genetic predisposition loci for metabolic syndrome., Methods: We studied 610 young adult volunteers (average age 24 yrs) for metabolic syndrome markers, and volumetric MRI of upper arm muscle, bone, and fat pre- and post-unilateral resistance training., Results: We found the PPARalpha L162V polymorphism to be a strong determinant of serum triglyceride levels in young White males, where carriers of the V allele showed 78% increase in triglycerides relative to L homozygotes (LL = 116 +/- 11 mg/dL, LV = 208 +/- 30 mg/dL; p = 0.004). Men with the V allele showed lower HDL (LL = 42 +/- 1 mg/dL, LV = 34 +/- 2 mg/dL; p = 0.001), but women did not. Subcutaneous fat volume was higher in males carrying the V allele, however, exercise training increased fat volume of the untrained arm in V carriers, while LL genotypes significantly decreased in fat volume (LL = -1,707 +/- 21 mm3, LV = 17,617 +/- 58 mm3 ; p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARalpha L162V is on serum triglycerides, with downstream effects on adiposity and response to training., Conclusion: Our results on association of PPARalpha and triglycerides in males showed a much larger effect of the V allele than previously reported in older and less healthy populations. Specifically, we showed the V allele to increase triglycerides by 78% (p = 0.004), and this single polymorphism accounted for 3.8% of all variation in serum triglycerides in males (p = 0.0037).

Purpose: It is believed spot reduction, the exercise-induced localized loss of subcutaneous fat, does not occur as a result of an exercise program; however, evidence as a whole has been inconsistent. To reexamine this concept, we compared subcutaneous fat measurements before and after resistance training among 104 subjects (45 men, 59 women)., Methods: Subjects participated in 12 wk of supervised resistance training of their nondominant arm. Magnetic resonance imaging and skinfold calipers examined subcutaneous fat in the nondominant (trained) and dominant (untrained) arms before and after resistance training. Repeated-measures ANCOVA tested for subcutaneous fat differences within and between arms before, after, and from before to after resistance training by gender and measurement technique, with BMI and age as covariates. Simple linear regression compared subcutaneous fat changes before and after resistance training as assessed by MRI and skinfold., Results: Subcutaneous fat, measured by skinfold, decreased in the trained arm and not the untrained arm in the men (P < 0.01); it was similar in the total sample and in the women (P > 0.05). MRI determinations of subcutaneous fat changes were not different between arms in the total sample and by gender (P > 0.05)., Conclusion: Subcutaneous fat changes resulting from resistance training varied by gender and assessment technique. Skinfold findings indicate that spot reduction occurred in men but not in women. In contrast, MRI found a generalized subcutaneous fat loss independent of gender, supporting the notion that spot reduction does not occur as a result of resistance training. MRI, sensitive to changes along the entire upper arm, detected greater variation in resistance training responses, preventing significant differences between trained and untrained arms. Variation in upper-arm resistance training response was not evident from a single skinfold measurement at the belly of the muscle.

Purpose: The purposes of this study were 1) derive allometric scaling models of isometric biceps muscle strength using pretraining body mass (BM) and muscle cross-sectional area (CSA) as scaling variables in adult males, 2) test model appropriateness using regression diagnostics, and 3) cross-validate the models before and after 12 wk of resistance training., Methods: A subset of FAMuSS (Functional SNP Associated with Muscle Size and Strength) study data (N=136) were randomly split into two groups (A and B). Allometric scaling models using pretraining BM and CSA were derived and tested for group A. The scaling exponents determined from these models were then applied to and tested on group B pretraining data. Finally, these scaling exponents were applied to and tested on group A and B posttraining data., Results: BM and CSA models produced scaling exponents of 0.64 and 0.71, respectively. Regression diagnostics determined both models to be appropriate. Cross-validation of the models to group B showed that the BM model, but not the CSA model, was appropriate. Removal of the largest six subjects (CSA>30 cm) from group B resulted in an appropriate fit for the CSA model. Application of the models to group A posttraining data showed that both models were appropriate, but only the body mass model was successful for group B., Conclusion: These data suggest that the application of scaling exponents of 0.64 and 0.71, using BM and CSA, respectively, are appropriate for scaling isometric biceps strength in adult males. However, the scaling exponent using CSA may not be appropriate for individuals with biceps CSA>30 cm. Finally, 12 wk of resistance training does not alter the relationship between BM, CSA, and muscular strength as assessed by allometric scaling.

Objective: The biological function of resistin (RST) is unknown, although it may have roles in obesity, diabetes, and insulin resistance. The objective of this study was to examine the effects of single nucleotide polymorphisms (SNPs) in the human RST gene on muscle, bone, and adipose tissue phenotypes and in response to resistance training (RT)., Research Methods and Procedures: Subjects were white and consisted of strength (n = 482) and size (n = 409) cohorts who had not performed RT in the previous year. Subjects completed 12 weeks of structured, unilateral upper arm RT aimed at increasing the size and strength of the non-dominant arm, using their dominant arm as an untrained control. Strength measurements were taken pre- and post-12-week RT and consisted of elbow flexor isometric strength and one-repetition maximum during a biceps curl using free weights. Whole muscle, subcutaneous fat, and cortical bone volumes were measured by magnetic resonance imaging. Six RST SNPs were identified. Analysis of covariance was used to test for effects of the SNPs on pre- and post-muscle strength and whole muscle, fat, and bone volumes independent of gender, age, and body weight., Results: Five RST SNPs (-537 A>C, -420 C>G, 398 C>T, 540 G>A, 980 C>G) were associated with measured phenotypes among subjects when stratified by BMI (<25, >/ or = 25 kg/m(2)). Several gender-specific associations were observed between RST SNPs and phenotypes among individuals with a BMI > or = 25. Conversely, only two associations were observed among individuals with a BMI < 25., Discussion: These data support previous identified associations of RST with adipose tissue and demonstrate additional associations with bone and skeletal muscle that warrant further investigation.

Purpose: To examine associations among the angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and the response to a 12-wk (2 d.wk) unilateral, upper-arm resistance training (RT) program in the trained (T, nondominant) and untrained (UT, dominant) arms., Methods: Subjects were 631 (mean+/-SEM, 24.2+/-0.2 yr) white (80%) men (42%) and women (58%). The ACE ID genotype was in Hardy-Weinberg equilibrium with frequencies of 23.1, 46.1, and 30.8% for ACE II, ID, and DD, respectively (chi=1.688, P=0.430). Maximum voluntary contraction (MVC) and one-repetition maximum (1RM) assessed peak elbow flexor muscle strength. Magnetic resonance imaging measured biceps muscle cross-sectional area (CSA). Multiple variable and repeated-measures ANCOVA tested whether muscle strength and size differed at baseline and pre- to post-RT among T and UT and ACE ID genotype., Results: Baseline muscle strength and size were greater in UT than T (P<0.001) and did not differ among ACE ID genotype in either arm (P >or= 0.05). In T, MVC increases were greater for ACE II/ID (22%) than DD (17%) (P<0.05), whereas 1RM (51%) and CSA (19%) gains were not different among ACE ID genotype pre- to post-RT (P >or= 0.05). In UT, MVC increased among ACE II/ID (7%) (P<0.001) but was similar among ACE DD (2%) pre- to post-RT (P >or= 0.05). In UT, 1RM (11%) and CSA (2%) increases were greater for ACE DD/ID than ACE II (1RM, 7%; CSA, -0.1%) (P<0.05). ACE ID genotype explained approximately 1% of the MVC response to RT in T and approximately 2% of MVC, 2% of 1RM, and 4% of CSA response in UT (P<0.05)., Conclusion: ACE ID genotype is associated with the contralateral effects of unilateral RT, perhaps more so than with the muscle strength and size adaptations that result from RT.

The alpha-actinin 3 (ACTN3) gene encodes a protein of the Z disk of myofibers, and a polymorphism of ACTN3 results in complete loss of the protein. The ACTN3 genotype (R577X) has been found to be associated with performance in Australian elite athletes (Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, and North K. Am J Hum Genet 73: 627-631, 2003). We studied associations between ACTN3 genotype and muscle size [cross-sectional area of the biceps brachii via magnetic resonance imaging (MRI)] and elbow flexor isometric (MVC) and dynamic [1-repetition maximum (1-RM)] strength in a large group of men (N = 247) and women (N = 355) enrolled in a 12-wk standardized elbow flexor/extensor resistance training program of the nondominant arm at one of eight study centers. We found no association between ACTN3 R577X genotype and muscle phenotype in men. However, women homozygous for the ACTN3 577X allele (XX) had lower baseline MVC compared with heterozygotes (P < 0.05) when adjusted for body mass and age. Women homozygous for the mutant allele (577X) demonstrated greater absolute and relative 1-RM gains compared with the homozygous wild type (RR) after resistance training when adjusted for body mass and age (P < 0.05). There was a trend for a dose-response with genotype such that gains were greatest for XX and least for RR. Significant associations were validated in at least one ethnic subpopulation (Caucasians, Asians) and were independent of training volume. About 2% of baseline MVC and of 1-RM strength gain after training were attributable to ACTN3 genotype (likelihood-ratio test P value, P = 0.01), suggesting that ACTN3 is one of many genes contributing to genetic variation in muscle performance and adaptation to exercise.

Heart failure (HF) is a slow progressive syndrome characterized by low cardiac output and peripheral metabolic, biochemical, and histological alterations. Protein loss and reduced protein turnover occur with aging, but the consequences of congestive HF (CHF) superimposed on the normal aging response are unknown. This study has two objectives: 1) to determine whether there was a difference between older age-matched controls and those with stable HF (i.e., ischemic pathology) in whole body protein turnover and 2) to determine whether protein metabolism in liver and skeletal muscle protein turnover is impacted by CHF. We measured the whole body protein synthesis rate with a U-(15)N-labeled algal protein hydrolysate in 10 patients with CHF and in 10 age-matched controls. Muscle fractional synthesis rate of lateral vastus muscle was determined with [U-(13)C]alanine on muscle biopsies obtained by a standard percutaneous needle biopsy technique. Fractional synthesis rates of five plasma proteins of hepatic origin (fibrinogen, complement C-3, ceruloplasmin, transferrin, and very low-density lipoprotein apoliprotein B-100) were determined by using (2)H(5)-labeled l-phenylalanine as tracer. Results showed that whole body protein synthesis rate was reduced in CHF patients (3.09 +/- 0.19 vs. 2.25 +/- 0.71 g protein x kg(-1) x day(-1), P < 0.05) as was muscle fractional synthesis rate (3.02 +/- 0.58 vs. 1.33 +/- 0.71%/day, P < 0.05) and very low-density lipoprotein apoliprotein B-100 (265 +/- 25 vs. 197 +/- 16%/day, P < 0.05). CHF patients were hyperinsulinemic (9.6 +/- 3.1 vs. 47.0 +/- 7.8 microU/ml, P < 0.01). The results were compared with those found with bed rest patients. In conclusion, protein turnover is depressed in CHF patients, and both skeletal muscle and liver are impacted. These results are similar to those found with bed rest, which suggests that inactivity is a factor in depressed protein metabolism.