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Background: In children, digital media, lifestyle, and the COVID pandemic have impacted sunlight exposure, exercise, and diet patterns - cues that entrain the circadian clock. We hypothesized that low morning cortisol reflects a weak circadian clock, impacting the pro-inflammatory state. The primary objective was to test relationships between diurnal cortisol fluctuations and the inflammatory state in children as a means of providing indirect support for this hypothesis., Methods: The Cardiovascular Health Intervention Program (CHIP) was a population-based cross-sectional and longitudinal study of circadian health in public elementary school children in Southern Maine, USA (recruitment period 2012-2017). Participants were 689 students in 4th grade (baseline; age=9.2 ± 0.4 years), and 647 students in 5th grade (age=10.5 ± 0.5 years). Nine salivary cortisol measures per child (2 awakening and 1 prior to bed for 3 sequential days) (n = 1336 child phenotype days; n = 7987 cortisol assays), 10 cytokines measured in morning and evening saliva samples (n = 202 child phenotype days), and lipids were measured. Clinical outcomes were blood pressure, weight and height (body mass index [BMI]; BMI = kg/m 2 ), among others., Findings: Upon-waking cortisol levels were 0.28 ± 0.13 µg/dL, 30-minute post-waking 0.33 ± 0.15 µg/dL, and evening 0.08 ± 0.10 µg/dL. Salivary cytokine levels (n = 202) showed interleukins (IL) IL-1β and IL-8 were highest in early morning (upon awakening; AM), and IL-6 and tumor necrosis factor (TNF) TNF-α highest before bed (PM) (IL-1β AM > PM [-4.02 fold; p < 0.001]; IL-8 AM > PM [-1.36 fold; p < 0.001]; IL-6 AM < PM [+1.49 fold; p < 0.001]; TNF-α AM < PM [+1.73 fold; p = 0.03]. Regression modeling showed high morning cortisol was associated with high morning IL-1β (p = 3.82 ×10 -6 ), but low evening IL-1β (p = 6.27 ×10 -4 ). Regression modeling of BMI z-score as the response variable showed the expected significant relationships to high density lipoprotein (HDL) (negative; p < 0.001), mean arterial pressure (positive; p < 0.001), and morning cortisol (negative; p = 0.01) but only weak relationships to either evening cortisol (p = 0.1) or cytokine (positive; p = 0.02; from the model with smallest Rsquared) levels., Interpretation: We provide preliminary data on diurnal fluctuations of inflammatory cytokines in saliva in a population-based cohort of children. Correlation of morning and evening cortisol levels with inflammatory cytokines in the same saliva samples showed that high morning cortisol was associated with high morning IL-1β and low evening IL-1β. Future studies may test the hypothesis that strong diurnal cycling of IL-1β may serve as a homeostatic mechanism keeping the immune system in check, and that low morning cortisol (possible circadian misalignment) may lead to less stringent control of inflammatory networks., Competing Interests: Declaration of Competing Interest The authors state that they have no conflicts of interest with the presented research., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Circadian cues in children (sunlight, exercise, diet patterns) may be associated with health outcomes. The primary objective was to assess associations of daily cortisol fluctuations (morning, night) with cardiovascular health outcomes. A secondary objective was to determine if 1-year longitudinal changes in circadian cortisol levels are associated with longitudinal changes in health outcomes., Study Design: The Cardiovascular Health Intervention Program (CHIP) was a cross-sectional and longitudinal study of cardiovascular risk profiles in public elementary school children in Southern Maine. Participants were 689 students in 4th grade (baseline; age = 9.20 ± 0.41 years), and 647 students in 5th grade (age = 10.53 ± 0.52 years). Longitudinal data (4th and 5th grade) was available for 347 participants. Clinical outcomes were blood pressure, hip/waist ratios, body mass index, percent fat. Laboratory measures were fasting glucose, lipids, and salivary cortisol measures (morning and evening)., Results: Lower first-in-morning diurnal cortisol levels were associated with increased blood pressure (β -0.23 ± 0.05; p < 0.001), increased body fat (β -0.22 ± 0.05; p < 0.001), and poor lipid profiles (β -0.15 ± 0.07; p < 0.05). Inclusion of night cortisol in the model (stress-related) improved associations of the model with bodyfat composition (morning β -0.27 ± 0.05; p < 0.001; night β +0.16 ± 0.06; p < 0.01). Adjustments for potential confounding variables improved associations of morning cortisol with lipids (β -0.19 ± 0.07; p < 0.01). Longitudinal analysis showed that lower morning diurnal cortisol in 4th grade was associated with increases in blood pressure a year later (β -0.18 ± 0.08; p = 0.017) after adjusting for confounding variables., Conclusion: Data presented suggest adding circadian misalignment (lower amplitude of first-in-morning cortisol) to existing models of metabolic syndrome in children. Further, circadian misalignment may be a factor contributing to high blood pressure., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Examinations related to divisional differences in the incidence of sports-related concussions (SRC) in collegiate ice hockey are limited., Purpose: To compare the epidemiologic patterns of concussion in National Collegiate Athletic Association (NCAA) ice hockey by sex and division., Study Design: Descriptive epidemiology study., Methods: A convenience sample of men's and women's ice hockey teams in Divisions I and III provided SRC data via the NCAA Injury Surveillance Program during the 2009-2010 to 2014-2015 academic years. Concussion counts, rates, and distributions were examined by factors including injury activity and position. Injury rate ratios (IRRs) and injury proportion ratios (IPRs) with 95% confidence intervals (CIs) were used to compare concussion rates and distributions, respectively., Results: Overall, 415 concussions were reported for men's and women's ice hockey combined. The highest concussion rate was found in Division I men (0.83 per 1000 athlete-exposures [AEs]), followed by Division III women (0.78/1000 AEs), Division I women (0.65/1000 AEs), and Division III men (0.64/1000 AEs). However, the only significant IRR was that the concussion rate was higher in Division I men than Division III men (IRR = 1.29; 95% CI, 1.02-1.65). The proportion of concussions from checking was higher in men than women (28.5% vs 9.4%; IPR = 3.02; 95% CI, 1.63-5.59); however, this proportion was higher in Division I women than Division III women (18.4% vs 1.8%; IPR = 10.47; 95% CI, 1.37-79.75). The proportion of concussions sustained by goalkeepers was higher in women than men (14.2% vs 2.9%; IPR = 4.86; 95% CI, 2.19-10.77), with findings consistent within each division., Conclusion: Concussion rates did not vary by sex but differed by division among men. Checking-related concussions were less common in women than men overall but more common in Division I women than Division III women. Findings highlight the need to better understand the reasons underlying divisional differences within men's and women's ice hockey and the need to develop concussion prevention strategies specific to each athlete population.

Introduction: There is an association between strength and health among adolescents, yet, what remains to be determined is sex-specific cut points for low strength in the detection of risk in this population. The purpose of this study was to determine thresholds of low grip strength in a large cohort (N=1,326) of adolescents., Methods: All data were collected between 2005 and 2008, and analyzed in 2014-2015. A cardiometabolic risk score (MetScore) was computed from the following components: percent body fat, fasting glucose, blood pressure, plasma triglyceride levels, and high-density lipoprotein cholesterol. A high-risk cardiometabolic phenotype was characterized as ≥75th percentile of the MetScore. Conditional inference tree analyses were used to identify sex-specific, low normalized strength (grip strength/body mass) thresholds and risk categories., Results: Lower strength was independently associated with increased odds of the high-risk cardiometabolic phenotype, such that for every 5% decrement of normalized strength, there were 1.48 and 1.45 increased odds (p<0.001) for boys and girls, even after adjusting for cardiorespiratory fitness and physical activity. Conditional tree analysis revealed a high-risk threshold for boys (≤0.33) and girls (≤0.28), as well as an intermediate threshold (boys, >0.33 and ≤0.45; girls, >0.28 and ≤0.36)., Conclusions: These sex-specific thresholds of low strength can be incorporated into a clinical setting for identifying adolescents that would benefit from lifestyle interventions to improve muscular fitness and reduce cardiometabolic risk., (Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

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.

Objectives: The purpose of this study was to determine the gender-specific independent association between muscular strength and cardiometabolic risk clustering in a large cohort (n = 1421) of children., Methods: Principal component analysis was used to determine the pattern of risk clustering and to derive a continuous aggregate score (MetScore) from various cardiometabolic risk components: percent body fat (%BF), fasting glucose, blood pressure, plasma triglycerides levels, and HDL-cholesterol. Gender-stratified risk and MetScore were assessed by using general linear models and logistic regression for differences between strength tertiles, as well as independent associations with age, BMI, estimated cardiorespiratory fitness (CRF), physical activity, and muscular strength (normalized for body mass)., Results: In both boys (n = 670) and girls (n = 751), there were significant differences in cardiometabolic profiles across strength tertiles, such that stronger adolescents had lower overall risk. Age, BMI, cardiorespiratory fitness, physical activity participation, and strength were all individually correlated with multiple risk components, as well as the overall MetScore. However, in the adjusted model, only BMI (β = 0.30), physical inactivity (β = 0.30), and normalized strength capacity (β = -1.5) emerged as significant (P < .05) predictors of MetScore. %BF was the strongest loading coefficient within the principal component analysis-derived MetScore outcome., Conclusions: Normalized strength is independently associated with lower cardiometabolic risk in boys and girls. Moreover, %BF was associated with all cardiometabolic risk factors and carried the strongest loading coefficient. These findings bolster the importance of early strength acquisition and healthy body composition in childhood.

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.

To develop a global view of muscle transcriptional differences between older men and women and sex-specific aging, we obtained muscle biopsies from the biceps brachii of young and older men and women and profiled the whole-genome gene expression using microarray. A logistic regression-based method in combination with an intensity-based Bayesian moderated t test was used to identify significant sex- and aging-related gene functional groups. Our analysis revealed extensive sex differences in the muscle transcriptome of older individuals and different patterns of transcriptional changes with aging in men and women. In older women, we observed a coordinated transcriptional upregulation of immune activation, extracellular matrix remodeling, and lipids storage; and a downregulation of mitochondrial biogenesis and function and muscle regeneration. The effect of aging results in sexual dimorphic alterations in the skeletal muscle transcriptome, which may modify the risk for developing musculoskeletal and metabolic diseases in men and women.

Background: The purpose of this study was to determine the sex-specific pattern of pediatric cardiometabolic risk with principal component analysis, using several biological, behavioral and parental variables in a large cohort (n = 2866) of 6th grade students., Methods: Cardiometabolic risk components included waist circumference, fasting glucose, blood pressure, plasma triglycerides levels and HDL-cholesterol. Principal components analysis was used to determine the pattern of risk clustering and to derive a continuous aggregate score (MetScore). Stratified risk components and MetScore were analyzed for association with age, body mass index (BMI), cardiorespiratory fitness (CRF), physical activity (PA), and parental factors., Results: In both boys and girls, BMI and CRF were associated with multiple risk components, and overall MetScore. Maternal smoking was associated with multiple risk components in girls and boys, as well as MetScore in boys, even after controlling for children's BMI. Paternal family history of early cardiovascular disease (CVD) and parental age were associated with increased blood pressure and MetScore for girls. Children's PA levels, maternal history of early CVD, and paternal BMI were also indicative for various risk components, but not MetScore., Conclusions: Several biological and behavioral factors were independently associated with children's cardiometabolic disease risk, and thus represent a unique gender-specific risk profile. These data serve to bolster the independent contribution of CRF, PA, and family-oriented healthy lifestyles for improving children's health.

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.)

Ankyrin repeat domain 6 (ANKRD6) is a ubiquitous protein that associates with early development in mammals and is highly expressed in the brain, spinal cord, and heart of humans. We examined the role of 8 ANKRD6 single-nucleotide polymorphisms (SNPs) on muscle performance and habitual physical activity (PA). Single-nucleotide polymorphisms were 545 T>A (rs9362667), 485 M>L (rs61736690), 233 T>M (rs2273238), 128 I>L (rs3748085), 631 P>L (rs61739327), 122 Q>E (rs16881983), 197805 G>A (rs9344950), and 710 L>X (NOVEL). This study consisted of 922 healthy, untrained, European-derived American men (n = 376, 23.6 ± 0.3 years, 25.0 ± 0.2 kg·m(-2)) and women (n = 546, 23.2 ± 0.2 years, 24.0 ± 0.2 kg·m(-2)). Muscle strength (maximum voluntary contraction [MVC] and 1 repetition maximum [1RM]) and size (cross-sectional area [CSA]) were assessed before and after 12 weeks of unilateral resistance training (RT). A subsample (n = 536, 23.4 ± 0.2 years, 24.6 ± 0.2 kg·m(-2)) completed the Paffenbarger Physical Activity Questionnaire. Associations among ANKRD6 genotypes and muscle phenotypes were tested with repeated measure analysis of covariance (ANCOVA) and PA phenotypes with multivariate ANCOVA, with age and body mass index as covariates. ANKRD6 122 Q>E was associated with increased baseline biceps CSA. ANKRD6 545 A>T and ANKRD6 710 L>X were associated with increased 1RM and MVC in response to RT, respectively. ANKRD6 631 P>L was associated with increased biceps CSA response to RT and time spent in moderate-intensity PA among the total sample and women. ANKRD6 genetic variants were associated with the muscle size and strength response to RT and habitual PA levels. Further research is needed to validate our results and explore mechanisms for the associations we observed.

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.

Previous studies have reported associations of polymorphisms in the IGF1 gene with phenotypes of body composition (BC). The purpose of this study was to identify phenotypes of BC and physical function that were associated with the IGF1 promoter polymorphism (rs35767, -C1245T). Subjects from the Health, Aging, and Body Composition Study, white males and females (n = 925/836) and black males and females (533/705) aged 70-79 years were genotyped for the polymorphism. Phenotypes of muscle size and function, bone mineral density, and BC were analyzed for associations with this polymorphism. To validate and compare these findings, a cohort of young (mean age = 24.6, SD = 5.9) white men and women (n = 173/296) with similar phenotypic measurements were genotyped. An association with BC was identified in elderly females when significant covariates (physical activity, age, smoking status, body mass index) were included. White women with C/C genotype had 3% more trunk fat and 2% more total fat than those with C/T (P < 0.05). Black women with C/C genotype had 3% less total lean mass and 3% less muscle mass than their T/T counterparts (P < 0.05). Associations were identified with muscle strength in white women (P < 0.01) that were in agreement with the C/C genotype having lower muscle function. Thus, in an elderly population but not a young population, a polymorphism in the IGF1 gene may be predictive of differences in body composition, primarily in black females.

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.

The purpose of this study was to assess the association of age with muscle mass and strength in a group of young adults before and after 12 weeks of progressive resistance training. Eight hundred twenty-six young males and females (age 24.34 +/- 5.69 yr, range 18-39 yr) completed a strictly supervised 12-week unilateral resistance training program of the nondominant arm. Isometric (maximal voluntary contraction [MVC]) and dynamic strength (1 repetition maximum [1RM]) of the elbow flexors and cross-sectional area (CSA) of the biceps-brachii using magnetic resonance imaging (MRI) scans were measured before and after training. Pearson correlation coefficients were calculated for size and strength variables and age. In addition, the cohort was divided into groups according to decade of life and differences assessed by analysis of variance. Age correlated significantly and positively with all pretraining measures of muscle size and strength (CSA: r = 0.191, p < 0.001; MVC: r = 0.109, p = 0.002; 1RM: r = 0.109, p = 0.002). Age was not related to the training-induced changes in CSA or MVC but was negatively associated with the change in 1RM (r = -0.217, p < 0.001). The study indicates that age does have a significant positive relationship with muscle size and strength in untrained young adults. Although age was negatively associated with improvements in 1RM, the effect of age was small relative to the improvements induced through resistance training, thus suggesting age does not limit response to training in any practical way during early adulthood.

A classic morphogen, bone morphogenetic protein 2 (BMP2) regulates the differentiation of pluripotent mesenchymal cells. High BMP2 levels promote osteogenesis or chondrogenesis and low levels promote adipogenesis. BMP2 inhibits myogenesis. Thus, BMP2 synthesis is tightly controlled. Several hundred nucleotides within the 3' untranslated regions of BMP2 genes are conserved from mammals to fishes indicating that the region is under stringent selective pressure. Our analyses indicate that this region controls BMP2 synthesis by post-transcriptional mechanisms. A common A to C single nucleotide polymorphism (SNP) in the BMP2 gene (rs15705, +A1123C) disrupts a putative post-transcriptional regulatory motif within the human ultra-conserved sequence. In vitro studies indicate that RNAs bearing the A or C alleles have different protein binding characteristics in extracts from mesenchymal cells. Reporter genes with the C allele of the ultra-conserved sequence were differentially expressed in mesenchymal cells. Finally, we analyzed MRI data from the upper arm of 517 healthy individuals aged 18-41 years. Individuals with the C/C genotype were associated with lower baseline subcutaneous fat volumes (P = 0.0030) and an increased gain in skeletal muscle volume (P = 0.0060) following resistance training in a cohort of young males. The rs15705 SNP explained 2-4% of inter-individual variability in the measured parameters. The rs15705 variant is one of the first genetic markers that may be exploited to facilitate early diagnosis, treatment, and/or prevention of diseases associated with poor fitness. Furthermore, understanding the mechanisms by which regulatory polymorphisms influence BMP2 synthesis will reveal novel pharmaceutical targets for these disabling conditions., ((c) 2009 Wiley-Liss, Inc.)

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.

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.

C-reactive protein (CRP) is a marker for systemic inflammation and increased cardiovascular disease risk. Regular exercise may decrease CRP. Apolipoprotein E (apo E) has 3 common genotype variants--E2/3, 3/3, and 3/4--that modulate lipid metabolism and may have other metabolic physiologic roles, including some evidence that the genotype affects CRP levels. We assessed fasting serum CRP in 117 (male = 51, female = 66) healthy adults who volunteered for a 6-month aerobic exercise program. Both pre- and posttraining measurements were available in 71 (male = 31, female = 40) subjects. At baseline and follow-up, the numbers of subjects in the 3 groups were approximately equal: 2/3, n = 33 and 20; 3/3, n = 41 and 26; and 3/4, n = 43 and 25. At baseline, CRP levels differed by apo E genotype: means +/- SD were 2.84 +/- 2.18, 2.59 +/- 2.34, and 1.90 +/- 2.13 mg/L for E2/3, 3/3, and 3/4 subjects, respectively (3/4 vs 2/3, P < .05). In women, CRP was higher than that in men (3.14 +/- 2.49 vs 2.12 +/- 2.13 mg/L, P < .006). Exercise failed to affect CRP in the entire cohort (2.68 +/- 2.38 vs 2.52 +/- 2.48 mg/L) or in any apo E genotype group, and the apo E genotype effect observed at baseline persisted after training. In a largely white study cohort, CRP is higher in apo E3/3 than in 3/4 subjects and in women compared with men, but remains unchanged by 6 months of standard aerobic exercise training of the volume and higher intensity promoted by national organizations to reduce cardiovascular disease risk. How apo E genotype affects CRP is not known.

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: 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.

Overweight and obesity result in musculoskeletal impairments that limit exercise capacity. We examined if the muscle strength and size response to resistance training (RT) differed among 687 young (mean +/- SEM, 24.2 +/- 0.2 years) overweight and obese (OW) compared to normal weight (NW) adults as denoted by the body mass index (BMI). Subjects were 449 NW (22.0 +/- 0.1 kg.m(-2), 23.4 +/- 0.3 years) and 238 OW (29.2 +/- 0.2 kg.m(-2), 25.6 +/- 0.4 years) men (n = 285) and women (n = 402) who underwent 12 weeks (2 d.wk(-1)) of RT of the nondominant arm. Maximum voluntary contraction (MVC) and 1 repetition maximum (1RM) assessed peak elbow flexor strength. Magnetic resonance imaging measured the biceps muscle cross sectional area (CSA). Multiple dependent variable analysis of covariance tested if muscle strength and size differed among BMI groups pre-, post-, and pre-to-post-RT. Overweight and obese had greater MVC, 1RM, and CSA than NW pre- and post-RT (p < 0.001). Maximum voluntary contraction and 1RM gains were not different between BMI groups pre- to post-RT (p >or= 0.05). When adjusted for baseline values, NW had greater relative MVC (21.2 +/- 1.0 vs. 17.4 +/- 1.4%) and 1RM (54.3 +/- 1.5 vs. 49.0 +/- 2.0%) increases than OW (p < 0.05). Normal weight also had greater allometric MVC (0.48 +/- 0.02 kg.kg(-0.67) vs. 0.40 +/- 0.03 kg.kg(-0.67)) and 1RM (0.25 +/- 0.00 vs. 0.22 +/- 0.01 kg.kg(-0.67)) gains than OW (p < 0.05). CSA gains were greater among OW than NW (3.6 +/- 0.2 vs. 3.2 +/- 0.1 cm(2)) (p < 0.001); however, relative CSA increases were not different between BMI groups (19.4 +/- 0.5 vs. 18.4 +/- 0.7%) (p >or= 0.05). Despite similar relative muscle size increases, relative and allometic strength gains were less among OW than NW. These findings indicate the short-term relative and allometric muscle strength response to RT may be attenuated among adults who are overweight and obese.

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.

A comparison of the leg-to-leg bioelectrical impedance (BIA) system and skinfold analysis in estimating % body fat in a large number of National Collegiate Athletic Association (NCAA) collegiate wrestlers was conducted. A series of 5 cross-sectional assessments, including the NCAA Division I and III Championships, were completed throughout the 1998-1999 wrestling season with samples ranging from (N = 90-274). Body density was determined from the 3 skinfold measures using the Lohman prediction equation. BIA measurements were determined using the Tanita body fat analyzer, model 305. Significant correlations between methods ranging from (r = 0.67-0.83, p < 0.001) and low standard error of estimates (SEE) for % body fat ranging from 2.1-3.5% were found throughout the 5 assessment periods. This preliminary study demonstrated that the leg-to-leg bioelectrical impedance system accurately estimated % body fat when compared to skinfolds in a diverse collegiate wrestling population.

In order to compare the influence of a single bout of exercise on HDL-C metabolism with normal variability, 12 male runners (mean age: 24.9 +/- 4 yr) who ran 15-30 miles per week underwent exercise (E) and control (C) experimental conditions. During the E trial subjects ran on a motor driven treadmill at 75% (42.5 +/- 4.7 ml.kg-1.min-1) VO2max until 800 Kcals were expended. The C trial consisted of no exercise. Subjects were instructed to follow the same diet and keep a four d food diary during each experimental condition. Fasted blood samples were obtained at the same time of day in each condition at time points corresponding to 24 h pre-exercise (24 PRE), 6 h post- (6 h) and 24 h post-exercise (24 h). Plasma was analyzed for HDL-C, HDL2-C and HDL3-C (mg.dl-1). In addition post-heparin plasma samples were analyzed for lipoprotein lipase (LPL) and hepatic lipase (HL) activity (mumol.FFA-1.ml-1). All values were adjusted for changes in plasma volume and compared to Baseline. HDL-C levels were unaltered following the C trial. However, following the E trial, HDL-C increased (p < 0.01) above baseline values at 24 h. The increase in HDL-C was reflected in the HDL3-C subfraction (p < 0.05). Analysis of lipolytic activity revealed an overall greater LPL activity (p < 0.05) in the E trial vs the C trial. In addition, a decrease in HL was observed at 24 h (p < 0.05) but was not different between experimental conditions. These data suggest that exercise and not normal variability are responsible for alterations in lipolytic activity and corresponding increases in HDL-C levels.

To investigate the effect of varying energy expenditure on acute high-density lipoprotein-cholesterol (HDL-C) changes, 12 healthy endurance-trained men completed three- counterbalanced running trials at different energy expenditures: trial 1, 1690.3 (24.4) kJ [mean (SD)]; trial 2, 2529.1 (24.0) kJ; trial 3, 3384.3 (36.6) kJ, with exercise intensity at 75% of maximal oxygen consumption. For each trial, blood samples were collected at 24 h pre-exercise (24 h Pre), immediately post-exercise, 1 h post-exercise, 6 h post-exercise (6 h PE), and 24 h post-exercise (24 h PE). Plasma samples were analyzed for HDL-C, HDL2-C and HDL3-C subfractions, and triglycerides (TG). In addition, post-heparin plasma samples were analyzed at 24 h Pre, 6 h PE and 24 h PE for lipoprotein lipase activity (LPLA) and hepatic triglyceride lipase activity. All samples were corrected for plasma volume changes and compared to 24 h Pre (baseline). When trials were combined, an increase (P < 0.05) in HDL-C was observed 24 h PE, via an increase (P < 0.05) in HDL3-C. An increase (P < 0.05) in LPLA and decrease (P < 0.05) in TG at 24 h PE is suggested to be responsible for the increase in HDL3-C. In conclusion, no difference in HDL-C was observed among trials. However, when trials were combined, an increase in HDL-C was observed, suggesting that an energy expenditure of no greater than 3384 kJ is needed to promote favorable changes in HDL-C.

To determine whether exercise intensity influences acute HDL-C responses, 12 male recreational runners (24.8 +/- 4 yr) who ran 15-30 miles.wk-1 exercised on a motor driven treadmill at 60% (L) and 75% (H) VO2max. A counterbalanced experimental design was utilized and energy expenditure was 800 Kcal. Fasting blood samples were obtained 24 h before exercise (24 PRE), immediately post-(IPE), 1 h post- (1 h PE), 6 h post- (6 h PE), and 24 h post- (24 h PE) exercise and analyzed for HDL-C and HDL2&3-C. In addition, postheparin plasma samples, obtained 24 h PRE, 6 h PE, and 24 h PE were analyzed for lipolytic activity--LPLA and HTGLA. An exercise trial by time interaction was observed for HDL-C (P < 0.01). Post-hoc analysis revealed no change in HDL-C following the L trial. However, an increase in HDL-C was observed 24 h PE (P < 0.01) following the H trial. The increase in HDL-C was attributed to an elevated HDL3-C (P < 0.01), with no change in HDL2-C. Analysis of plasma lipolytic activity revealed an increase in LPLA 24 h PE (P < 0.05) which may be responsible for the postexercise alterations in HDL-C. However, HTGLA decreased 6 h PE (P < 0.01) and 24 h PE (P < 0.05). We conclude that increases in HDL-C levels following endurance activity are influenced, in part, by the exercise intensity.