Publications

Maximal oxygen uptake (VO2max) is one of the most important determinants of elite endurance performance. VO2max is determined by a whole range of genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in muscle myostatin (MSTN) and creatine kinase (CKM) genes are candidates for VO2max and skeletal muscle performance phenotypes. Common MSTN (rs3791783, rs11681628 and rs7570532) and CKM (rs344816, rs10410448, rs432979, rs1133190, rs7260359, rs7260463 and rs4884) SNPs, selected from HapMap CEU data in order to tag the genetic variability of the proteins, were genotyped in 316 male Caucasian elite endurance athletes and 304 sedentary controls from the Genathlete study. Association with elite endurance performance was determined by logistic regression analysis. The P-value for statistical significance was set at <0.01. None of the SNPs or haplotypes showed a significant association with elite endurance status. We conclude that common variants of MSTN and CKM genes do not play a role in attaining high-level endurance performance in Caucasian populations.

The relation of daily energy expenditure (EE) and maximal oxygen uptake(˙VO2max) to plasma fibrinogen with reference to DNA polymorphism was analyzed in a random sample of men (N = 189), age 50-60. Fibrinogen polymorphism was detected using polymerase chain reaction (PCR) and digestion with HindIII and BclI (β-fibrinogen), and TaqI(α-fibrinogen) restriction enzymes. Mean ˙VO2max was 29.4 ml·kg-1·min-1 (95%CI 28.5; 30.2) and mean daily EE was 179 kJ·kg-1·d-1 (173; 186) and were similar in all fibrinogen genotypes. Plasma fibrinogen was 3.26 g·l-1(3.18; 3.34) and did not associate with fibrinogen polymorphisms. Both EE and˙VO2max related inversely to fibrinogen level (r = -0.24,P < 0.001). Strongest predictors of plasma fibrinogen were˙VO2max in TaqI 800 bp homozygotes, and EE together with smoking in TaqI 900 bp homozygotes. The predictive role of ˙VO2max was marginal in the common β-fibrinogen genotypes, whereas physical activity level explained up to 9% of the variance in the less frequent genotypes. These data suggest that the association of ˙VO2max and EE with plasma fibrinogen varies across the fibrinogen genotypes.

The beneficial effects of physical activity (PA) are well documented, yet the mechanisms by which PA prevents disease and improves health outcomes are poorly understood. To identify major gaps in knowledge and potential strategies for catalyzing progress in the field, the NIH convened a workshop in late October 2014 entitled “Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits.” Presentations and discussions emphasized the challenges imposed by the integrative and intermittent nature of PA, the tremendous discovery potential of applying “-omics” technologies to understand interorgan crosstalk and biological networking systems during PA, and the need to establish an infrastructure of clinical trial sites with sufficient expertise to incorporate mechanistic outcome measures into adequately sized human PA trials. Identification of the mechanisms that underlie the link between PA and improved health holds extraordinary promise for discovery of novel therapeutic targets and development of personalized exercise medicine.

Ghrelin and preproghrelin sequences were determined in 96 unrelated female subjects with severe obesity (mean body mass index (BMI) 42.3 +/- 3.4 kg/m(2)) and in 96 non-obese female controls (mean BMI 23.0 +/- 1.4 (kg/m2) of the Swedish Obese Subjects cohort. A mutation at amino acid position 51 (Arg51Gln) of the preproghrelin sequence that corresponds to the last amino acid in mature ghrelin product was identified in six (all heterozygotes) obese subjects (6.3%) but not among controls (p < 0.05). The self-reported weight at 20, 30, and 40 years of age tended to be 7.5, 4.7 and 6.4 kg lower, respectively, among obese Gln allele carriers versus obese non-carriers. In addition, a mutation at codon 72 of the preproghrelin gene (Leu72Met) was detected in 15 obese (12 hetero- and 3 homozygotes) and 12 control (all heterozygotes) subjects. This mutation outside the coding region of the mature ghrelin product tended to be associated with lower age of self-reported onset of obesity (15.6 +/- 7.9 vs. 20.5 +/- 10.5 years; p = 0.09). In addition to these two mutations in coding regions, a G274A base change in a non-coding region between exons one and two was found only in two obese individuals. The Arg51Gln amino acid substitution may alter the cleavage site of endoproteases and the length of the mature ghrelin product. The functional significance of the Leu72Met mutation and a G274A base change remains to be determined. In conclusion, the data provide evidence that a low frequency sequence variation in the ghrelin gene could play a role in the etiology of obesity.

To investigate whether greater cardiorespiratory fitness (CRF) is associated with better cognitive function 25 years later.We studied 2,747 participants in the community-based Coronary Artery Risk Development in Young Adults Study of black and white men and women aged 18 to 30 years at recruitment in 1985-1986 (baseline year 0). Symptom-limited maximal treadmill test durations at years 0 and 20 provided measures of CRF. Cognitive tests at year 25 measured verbal memory (Rey Auditory Verbal Learning Test [RAVLT]), psychomotor speed (Digit Symbol Substitution Test [DSST]), and executive function (Stroop Test).Per minute of baseline CRF, the RAVLT was 0.12 words recalled higher (standard error [SE] = 0.03, p < 0.0001), the DSST was 0.92 digits higher (SE = 0.13, p < 0.0001), and the Stroop Test score was 0.52 lower (better performance, SE = 0.11, p < 0.0001), after accounting for race, sex, age, education, and clinical center. Compared with the lowest quartile of CRF, each cognitive test was 21% to 34% of an SD better in the highest CRF quartile. Further adjustment for lifestyle and clinical measures attenuated coefficients for RAVLT and DSST slightly, while the coefficient predicting the Stroop Test lost more than half its value (p = 0.07). Analysis in the subset of 1,957 participants who also completed the year-20 treadmill test showed that 20-year change in CRF was positively associated only with DSST (p < 0.001).Better verbal memory and faster psychomotor speed at ages 43 to 55 years were clearly associated with better CRF 25 years earlier.

No abstract is provided for this article.

GREEN, J. S., P. R. STANFORTH, J. GAGNON, A. S. LEON, D. C. RAO, J. S. SKINNER, C. BOUCHARD, T. RANKINEN, and J. H. WILMORE. Menopause, estrogen, and training effects on exercise hemodynamics: the HERITAGE study. Med. Sci. Sports Exerc., Vol. 34, No. 1, 2002, pp. 74–82. Purpose To investigate the influences of menopause, hormone replacement, and endurance exercise training on cardiovascular hemodynamics and oxygen uptake parameters during exercise in women. Methods Subjects were 338 premenopausal women, 29 postmenopausal women taking hormone replacement, and 28 postmenopausal women not taking hormone replacement, all enrolled in the HERITAGE Family Study. Hemodynamic and oxygen uptake data were gathered on a cycle ergometer at 50 watts (W), 60% peak oxygen uptake, and at peak exercise, both before and after a 20-wk regimen of endurance exercise training on a cycle ergometer. Results Systolic blood pressure (SBP) during peak exercise was found to be an average of 14 mm Hg less in postmenopausal women receiving hormones than in those not receiving hormones. Furthermore, menopause was associated with a 26.2 mm Hg higher SBP at 50 W power output, which remained physiologically significant after adjustment for age. At 50 W, postmenopausal women not taking hormones showed a 13.8 mm Hg greater training-induced reduction in SBP than those taking hormones. Conclusion It was concluded that hormone replacement may be associated with a vasodilatory reserve at high exercise intensities and that endurance exercise training elicits favorable hemodynamic and oxygen uptake adaptations during exercise that are, in most instances, independent of menstrual status or hormone replacement.

Background: Excessive visceral fat is associated with metabolic alterations and is a causal risk factor for CVD. The plasma lipidome is altered in obesity and lipidome signatures of BMI and obesity have been identified. However, few studies have examined the plasma lipidome in relation to visceral fat. Methods: Plasma lipids were measured using the C8-positive LC-MS method in 671 participants from the HERITAGE Family Study (56% Female, 35% Black, 35 yrs). Visceral fat was measured using CT scans. Linear mixed models were used to test the associations of 193 known plasma lipids with visceral fat adjusting for age, sex, race, and BMI. A FDR&lt;5% was used to determine significance. Results: In individual models, 156 lipid species were significantly associated with visceral fat, with 109 species associated after additional adjustment for BMI ( Fig 1 ). The top positively associated lipids were triglycerides, while cholesterol esters showed the strongest inverse associations with visceral fat. A LASSO regression model retained 73 lipids and explained 78.5% of the variance in visceral fat. Delta visceral fat was calculated as the difference between predicted (from LASSO) and measured visceral fat. Examining quartiles of delta visceral fat showed that discordance between predicted and actual visceral fat was associated with differing cardiometabolic profiles independent of age, sex, race, visceral fat, and BMI. Individuals with higher delta visceral fat (Q4, overpredicted) had significantly (p&lt;1.0x10 -04 ) higher levels of TG, apoB, total cholesterol, LDL-C, and fasting insulin and lower levels of large HDL particles and LPL activity compared to those with lower delta visceral fat (Q1, underpredicted). Conclusions: The plasma lipidome is widely associated with visceral fat levels. A lipidome-based visceral fat score may provide additional information over measured visceral fat for assessment of cardiometabolic health. Further studies are needed to test and validate the clinical utility of such lipidome-based scores.

In the present investigation, we have attempted to identify regions of the genome in which “obesity genes” potentially reside using robust sib‐pair linkage analysis. Data were collected on 1,628 individuals in 301 nuclear families residing in the environs of Québec City during the period 1978–1981. In addition to traditional blood group antigens and enzyme polymorphisms, several phenotypes in the obesity domain that are associated with increased morbidity were assessed, including measures relating to heaviness (i.e., the body mass index), body composition and nutrient partitioning (i.e., % body fat), and regional fat distribution without and with standardization for total fat mass (i.e., the sum of six skinfold thicknesses, and the ratio of the sums of trunk to extremity skinfold thicknesses). Three consistent patterns of potential linkage relationships with obesity phenotypes were revealed in these data, involving the marker loci adenosine deaminase, the Kell blood group antigen, and esterase D, which identify chromosomal regions 20q13, 7q33, and 13q14, respectively. Other potential linkages also were identified in the short arm of chromosome 1, interesting because of the presence of the db and fa loci on homologous regions of chromosome 1 in mouse and rat models of obesity, respectively. Each of the tentative linkage relationships reported here warrant follow‐up using alternative methods and require replication in independent studies.

A DNA sequence variant in the K+ voltage-gated channel of the shaw related subfamily member 1 (KCNC1) gene (11p15) is known to be associated with VO2max in the sedentary and trained states in Blacks, but not in Whites (MSSE 36(5), S99, 2003). PURPOSE To examine the association between the same KCNC1 gene polymorphism and endurance performance level in a cohort of Hispanics. METHODS The polymorphism was detected by PCR and digestion with MspI in 302 DNA samples from Hispanic marathon runners (n=225) and cardiac patients (n = 77). They were divided into three groups according to endurance performance level. Cases (C; n = 105) and active controls (AC; n = 120), were long-distance runners finishers in the highest and lowest 3 percentile, by age and gender respectively, during an international marathon (42 km) race, while controls (CON; n = 77) were intensive care coronary unit subjects with severely compromised cardiorespiratory functions. RESULTS The observed KCNC1 genotypic frequencies for both genders were in Hardy-Weinberg equilibrium (X2, P>0.05). X2 analysis showed that neither allelic nor genotype frequencies were significantly (P>0.05) different between genders or groups. The pooled genotypic and allelic data is shown in the table below.TableCONCLUSION The present findings do not provide support for the notion that the K+ voltage-gated channel of the shaw related subfamily member 1 is associated with endurance performance status in Hispanics. Supported by CRC-RCMI 1P20RR11126, RCMI #G12RR03051, Comite de Fondismo: FPRA, Maraton Pacifico, Maraton de Guadalajara, and Maraton Popular de Madrid.

Prospective studies have shown that excess abdominal fat is associated with an increased risk of coronary heart disease and related death. We used computed axial tomography (CAT) to assess the association between deep and subcutaneous abdominal adipose tissue and plasma lipoprotein levels in a sample of 52 premenopausal obese women aged 35.7 +/- 5.5 years (mean +/- SD). Whereas the plasma lipoprotein concentration were not significantly correlated with fat mass, the data obtained by CAT indicated that the absolute amount of deep abdominal fat was negatively correlated with high density lipoprotein cholesterol (HDL-CHOL) levels (r = -0.35, p less than 0.01), as well as with HDL-CHOL/low density lipoprotein (LDL)-CHOL, HDL-apoprotein-(apo) A-I/LDL-apo B, and HDL2-CHOL/HDL3-CHOL ratios (-0.32 less than or equal to r less than or equal to -0.40, 0.05 greater than p less than 0.01). Adipose tissue deposition at the mid-thigh region determined by CAT did not show any significant relationship with plasma lipoprotein levels. When subgroups of women with comparable ages and adiposity but with high and low intra-abdominal fat accumulation were compared, women with a high accumulation of intra-abdominal fat displayed significantly lower HDL-CHOL (p less than 0.001), HDL2-CHOL (p less than 0.001), HDL3-CHOL (p less than 0.01), and HDL-apo A-I (p less than 0.05) levels, as well as reduced HDL-CHOL/LDL-CHOL (p less than 0.01), HDL-apo A-I/LDL-apo B (p less than 0.05), and HDL2-CHOL/HDL3-CHOL ratios (p less than 0.05) in comparison with obese women with low accumulations of intra-abdominal fat.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract is provided for this article.