No abstract is provided for this article.
Low cardiorespiratory fitness is a powerful predictor of morbidity and cardiovascular mortality. In 473 sedentary adults, all whites, from 99 families of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, the heritability of gains in maximal O(2) uptake (VO(2max)) after exposure to a standardized 20-wk exercise program was estimated at 47%. A genome-wide association study based on 324,611 single-nucleotide polymorphisms (SNPs) was undertaken to identify SNPs associated with improvements in VO(2max) Based on single-SNP analysis, 39 SNPs were associated with the gains with P < 1.5 × 10(-4). Stepwise multiple regression analysis of the 39 SNPs identified a panel of 21 SNPs that accounted for 49% of the variance in VO(2max) trainability. Subjects who carried ≤9 favorable alleles at these 21 SNPs improved their VO(2max) by 221 ml/min, whereas those who carried ≥19 of these alleles gained, on average, 604 ml/min. The strongest association was with rs6552828, located in the acyl-CoA synthase long-chain member 1 (ACSL1) gene, which accounted by itself for ~6% of the training response of VO(2max). The genes nearest to the SNPs that were the strongest predictors were PR domain-containing 1 with ZNF domain (PRDM1); glutamate receptor, ionotropic, N-methyl-D-aspartate 3A (GRIN3A); K(+) channel, voltage gated, subfamily H, member 8 (KCNH8); and zinc finger protein of the cerebellum 4 (ZIC4). The association with the SNP nearest to ZIC4 was replicated in 40- to 65-yr-old, sedentary, overweight, and dyslipidemic subjects trained in Studies of a Targeted Risk Reduction Intervention Through Defined Exercise (STRRIDE; n = 183). Two SNPs were replicated in sedentary obese white women exercise trained in the Dose Response to Exercise (DREW) study (n = 112): rs1956197 near dishevelled associated activator of morphogenesis 1 (DAAM1) and rs17117533 in the vicinity of necdin (NDN). The association of SNPs rs884736 in the calmodulin-binding transcription activator 1 (CAMTA1) locus and rs17581162 ~68 kb upstream from regulator of G protein signaling 18 (RGS18) with the gains in VO(2max) in HERITAGE whites were replicated in HERITAGE blacks (n = 247). These genomic predictors of the response of Vo(2max) to regular exercise provide new targets for the study of the biology of fitness and its adaptation to regular exercise. Large-scale replication studies are warranted.
CLASEY, JODY L., CLAUDE BOUCHARD, C. DAVID TEATES, JILL E. RIBLETT, MICHAEL O. THORNER, MARK L. HARTMAN, AND ARTHUR WELTMAN. the use of anthropometric and dual‐energy X‐ray absorptiometry (DXA) measures to estimate total abdominal and abdominal visceral fat in men and women. Obes Res . Objective : A single‐slice computed tomography (CT) scan provides a criterion measure of total abdominal fat (TAF) and abdominal visceral fat (AVF), but this procedure is often prohibitive due to radiation exposure, cost, and accessibility. In the present study, the utility of anthropometric measures and estimates of trunk and abdominal fat mass by dual‐energy X‐ray absorptiometry (DXA) to predict CT measures of TAF and AVF (cross‐sectional area, cm 2 ) was assessed. Research Methods and Procedures : CT measures of abdominal fat (at the level of the L4‐L5 inter‐vertebral space), DXA scans, and anthropometric measures were obtained in 76 Caucasian adults ages 20–80 years. Results : Results demonstrated that abdominal sagittal diameter measured by anthropometry is an excellent predictor of sagittal diameter measured from a CT image (r = 0. 88 and 0. 94; Total Error [TE]=4. 1 and 3. 1 cm, for men and women, respectively). In both men and women, waist circumference and abdominal sagittal diameter were the anthropometric measures most strongly associated with TAF (r = 0. 87 to 0. 93; Standard Error of Estimate (SEE) = 60. 7 to 75. 4 cm 2 ) and AVF (r = 0. 84 to 0. 93; SEE = 0. 7 to 30. 0 cm 2 ). The least predictive anthropometric measure of TAF or AVF was the commonly used waist‐to‐hip ratio (WHR). DXA estimates of trunk and abdominal fat mass were strongly associated with TAF ( r =. 94 to 0. 97; SEE = 36. 9 to 50. 9 cm 2 ) and AVF ( r = 0. 86 to 0. 90; SEE = 4. 9 to 27. 7 cm 2 ). Discussion : The present results suggest that waist circumference and/or abdominal sagittal diameter are better predictors of TAF and AVF than the more commonly used WHR. DXA trunk fat and abdominal fat appear to be slightly better predictors of TAF but not AVF compared to these anthropometric measures. Thus DXA does not offer a significant advantage over anthropometry for estimation of AVF.
THE ROLE of inherited and nongenetic factors in individual differences observed in the level of sc fat on the trunk and abdominal areas and in the abdominal visceral deposit is reviewed. First, the metabolic and clinical implications of variation in body fat topography are summarized. Second, the results of genetic epidemiology studies on the heritability and other evidence for a role of the genotype in the amount of truncal-abdominal sc fat and abdominal visceral fat are reviewed. Third, the impact of total body fat, age, and gender on regional fat distribution is highlighted. Fourth, adipose tissue lipoprotein lipase activity is considered as a determinant of fat topography, with a discussion of site and gender differences, the effects of steroid hormones, and evidence from genetic epidemiology. Fifth, the contribution of adipose tissue lipolysis is reviewed with an emphasis on the various regulatory factors of the lipolytic pathways including catecholamines, insulin, adenosine, steroids, and other modulators. The role of lipolytic characteristics on fat topography is further assessed by considering changes with age, differences between men and women, effects of excess body fat, and data from heritability studies. Although the study of regional variation of in vitro adipose tissue metabolism has provided valuable information, a better understanding of variation in fat topography and of the role played by adipose tissue in the regulation of whole body carbohydrate and lipid metabolism will likely require extensive in situ and in vivo investigations. Sixth, as enlargement of a specific fat deposit is associated with increases in fat cell size and number, these topics are considered with an emphasis on the role of adipose cell differentiation. Seventh, the importance of blood levels of sex steroids and glucocorticoids for regional fat distribution is discussed. Then, a unifying hypothesis, defined as the hypothalamic arousal and neuroendocrine dysregulation model, is briefly described. Finally, the issue of whether body fat distribution can be altered by caloric restriction or regular exercise is addressed.