Publications

Adiponectin (also called AdipoQ, gelatin-binding protein 28, Acrp30) DNA sequence variants were determined in 96 unrelated female subjects with severe obesity (mean body mass index [BMI], 42.3 kg/m2) and in 96 non-obese female controls (mean BMI, 23.0 kg/m2) from the Swedish Obese Subjects (SOS) cohort. A single base substitution (T45G) at codon 15 of exon 2 resulting in no change in amino acid (Gly15Gly) was found in equal frequencies among obese and control subjects. However, this polymorphism was associated with serum cholesterol and waist circumference (P = .023 and .043, respectively) in the obese group. A IVS2 + G62T sequence variation was also identified, but had similar prevalence rates in obese and control subjects. Blood glucose was highest in the obese female subjects who were homozygotes for the G allele (GG) of the IVS2 + G62T polymorphism (N = 56; P = .033) and all the diabetics (n = 6) in this sample were in this group. IVS2 + G62T polymorphism was also associated with BMI (P = .014), diastolic blood pressure (P = .009), and sagittal diameter (P = .032). A missense point mutation at codon 111 (Tyr111His) was not associated with any obesity-related phenotypes. In conclusion, adiponectin DNA sequence variations might play a role in the complications of morbid obesity and should be further investigated.

Background and aims GlycA is a relatively new biomarker for inflammation as well as cardiometabolic disease risk. However, the effect of exercise on GlycA is largely unknown. Therefore, the purpose of this study was to examine the effects of regular exercise on the inflammatory marker GlycA across seven studies and 14 exercise interventions. Methods Nuclear magnetic resonance spectroscopy, specifically signal amplitudes originating from the N-acetyl methyl group protons of the N-acetylglucosamine residues on the glycan branches of glycoproteins, was used to quantify GlycA concentrations. GlycA was measured before and after completion of an exercise intervention in 1568 individuals across seven studies and 14 exercise interventions. Random effects inverse variance weighting models were used to pool effects across interventions. Results Combined analysis of unadjusted data showed that regular exercise significantly (p = 2 × 10−6) reduced plasma GlycA (−8.26 ± 1.8 μmol/L). This reduction remained significant (−9.12 ± 1.9 μmol/L, p = 1.22 × 10−6) following adjustment for age, sex, race, baseline BMI, and baseline GlycA. Changes in GlycA were correlated with changes in traditional inflammatory markers, C-reactive protein, interleukin-6, and fibrinogen, however, these correlations were relatively weak (range r: 0.21–0.38, p < 0.0001). Conclusions Regular exercise significantly reduced plasma GlycA across 14 different exercise interventions despite differences in exercise programs and study populations. The current study provides a greater understanding of the use of exercise as a potential therapy for the reduction of systemic inflammation. Further research is needed to understand the mechanisms behind the exercise-related reductions in GlycA.

Background: Metabolic risk varies within adult body mass index (BMI) categories; however, the development of BMI-specific metabolic risk from childhood is unknown. Methods: The sample included 895 adults (20–38 years of age; 43% male, 34% black) from the Bogalusa Heart Study (1995–2002), who had been measured as children (5–18 years of age) in 1981–1982. Adult metabolic risk was assessed using two definitions: Cardiometabolic risk factor clustering (RFC) included two or more abnormal risk factors [blood pressure, high-density lipoprotein cholesterol (HDL-C), triglycerides, and fasting glucose] and insulin resistance (IR), comprising the top quartile of the homeostasis model of insulin resistance (HOMA-IR) distribution. Logistic regression, within BMI categories, was used to predict adult metabolic risk from childhood mean arterial pressure (MAP), HDL-C, low-density lipoprotein cholesterol (LDL-C), glucose, and triglycerides. Covariates included childhood age, race, sex, adult BMI, and length of follow-up. Results: The prevalence of the adult abnormal metabolic risk profile varied by definitions of metabolic risk (normal weight, 5%–9%; overweight, 15%–23%; and obese, 40%–53%). The adult abnormal profile was associated with higher childhood LDL-C [IR, odds ratio (OR), 1.95; 95% confidence interval (CI), 1.06–3.58) and insulin (IR, OR, 1.69; CI, 1.10–2.58) in normal-weight adults; lower childhood HDL-C in overweight adults (RFC, OR, 0.61; CI, 0.40–0.94); and higher childhood MAP (RFC, OR, 1.75; CI, 1.24–2.47) and glucose (IR, OR,1.38; CI, 1.06–1.81) in obese adults. Conclusions: Some childhood metabolic risk factors are moderately associated with adult BMI-specific metabolic risk profiles. The ability to identify children with high future adult cardiovascular risk may initiate early treatment options.

Background: The assessment of fat mass and fat-free mass in relation to the symptom-limited maximal exercise duration (Maxdur) of a treadmill test allows for insight into the association of body composition with treadmill performance potential. Objective: We investigated the complex associations between fat mass and fat-free mass and Maxdur in a population setting. Design: The Maxdur of a graded exercise treadmill test and body composition by dual-energy X-ray absorptiometry were estimated in 2413 black and white men and women aged 38–50 y from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Results: The mean Maxdur was ≈7.5 s shorter per kilogram of fat mass in both men and women and independent of fat-free mass, height, race, television watching, physical activity, systolic blood pressure, lung function, and education. Fat mass modified the association of fat-free mass with the Maxdur (2-way interaction P < 0.001), and the interaction was stronger in women than in men. In men in the lowest fat-mass quartile, the Maxdur was 1.3 s longer per kilogram of fat-free mass and was 0.5 s shorter per kilogram of fat-free mass in the highest fat-mass quartile. In contrast, in women with the least fat mass, the Maxdur was 2.7 s longer per kilogram of fat-free mass and was 2.8 s shorter per kilogram of fat-free mass in the highest fat-mass quartile. Conclusions: The Maxdur was negatively related to fat mass. Fat-free mass in obese people contributed little to the treadmill performance potential as assessed by the Maxdur, although the contribution of fat-free mass was positive in thinner people.

This report constitutes the eighth update of the human obesity gene map, incorporating published results up to the end of October 2001. Evidence from the rodent and human obesity cases caused by single‐gene mutations, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci (QTLs) uncovered in human genome‐wide scans and in crossbreeding experiments in various animal models, association and linkage studies with candidate genes and other markers is reviewed. The human cases of obesity related in some way to single‐gene mutations in six different genes are incorporated. Twenty‐five Mendelian disorders exhibiting obesity as one of their clinical manifestations have now been mapped. The number of different QTLs reported from animal models currently reaches 165. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 174 studies reporting positive associations with 58 candidate genes. Finally, 59 loci have been linked to obesity indicators in genomic scans and other linkage study designs. The obesity gene map depicted in Figure 1 reveals that putative loci affecting obesity‐related phenotypes can be found on all chromosomes except chromosome Y. A total of 54 new loci have been added to the map in the past 12 months, and the number of genes, markers, and chromosomal regions that have been associated or linked with human obesity phenotypes is now above 250. Likewise, the number of negative studies, which are only partially reviewed here, is also on the rise.

This study investigated different methods of scaling submaximal cardiac output (Q) and stroke volume (SV) to best normalize for body size (body surface area [BSA], height [Ht], weight [Wt], and fat-free mass [FFM]). Q and SV were measured at both an absolute (50 W) and a relative power output (60 % of V·O2max) in 337 men and 422 women, 17 to 65 years of age. Traditional ratio scaling was examined in addition to allometric scaling, where scaling exponents (b) were determined for each body size variable (x) that best normalized the physiological outcome variables (y) for body size (y = ax b ). With ratio scaling, regardless of the body size variable (x = BSA, Ht, Wt, FFM), there was no evidence of a linear relationship between x and y (y = Q or SV). A linear relationship is a necessary condition for appropriate normalization. Further, when ratio-scaled variables (e.g., Q/BSA) were correlated to the body size variable (e.g., BSA) by which they were scaled, significant (p ≤ 0.05) relationships still existed for BSA, Ht, Wt, and FFM. Thus, ratio scaling did not meet either criteria for normalizing Q and SV for body size. In contrast, when allometrically-derived scaling exponents were used to normalize Q and SV (e.g., Q/BSA b ), the resulting scaled values were uncorrelated (i.e., size-independent) with BSA, Ht, Wt, or FFM. These results were independent of age, sex or race. In summary, ratio scaling did not appropriately normalize Q and SV for differences in body size, while allometric scaling did result in size-independent values. Thus, individually-derived allometric exponents should be applied to body size variables to most appropriately adjust Q and SV for body size.

The Na + -K + -ATPase plays an important role in the maintenance of electrolyte balance in the working muscle and thus may contribute to endurance performance. This study aimed to investigate the associations between genetic variants at the Na + -K + -ATPase α2 locus and the response (Δ) of maximal oxygen consumption (V˙o 2 max ) and maximal power output (W˙ max ) to 20 wk of endurance training in 472 sedentary Caucasian subjects from 99 families. V˙o 2 max andW˙ max were measured during two maximal cycle ergometer exercise tests before and again after the training program, and restriction fragment length polymorphisms at the Na + -K + -ATPase α2 (exons 1 and 21–22 with Bgl II) gene were typed. Sibling-pair linkage analysis revealed marginal evidence for linkage between the α2 haplotype and ΔV˙o 2 max ( P= 0.054) and stronger linkages between the α2 exon 21–22 marker ( P = 0.005) and α2 haplotype ( P = 0.003) and ΔW˙ max . In the whole cohort, ΔV˙o 2 max in the 3.3-kb homozygotes of the exon 1 marker ( n = 5) was 41% lower than in the 8.0/3.3-kb heterozygotes ( n = 87) and 48% lower than in the 8.0-kb homozygotes ( n = 380; P = 0.018, adjusted for age, gender, baselineV˙o 2 max , and body weight). Among offspring, 10.5/10.5-kb homozygotes ( n = 14) of the exon 21–22 marker showed a 571 ± 56 (SE) ml O 2 /min increase inV˙o 2 max , whereas the increases in the 10.5/4.3-kb ( n = 93) and 4.3/4.3-kb ( n= 187) genotypes were 442 ± 22 and 410 ± 15 ml O 2 /min, respectively ( P = 0.017). These data suggest that genetic variation at the Na + -K + -ATPase α2 locus influences the trainability ofV˙o 2 max in sedentary Caucasian subjects.

Background: Body composition is known to differ across metabolic health and weight phenotypes. Regular exercise improves body composition, yet little is known about differences in exercise response across metabolic health and weight phenotypes. Methods: Normal weight (n=376) and overweight/obese (OWOB) adults (n=456) from the HERITAGE Family Study (56% female, 38% Black) completed a 20-week endurance training program. Four groups based on baseline BMI and metabolic risk were created: metabolically healthy normal weight, MHNW; metabolically unhealthy normal weight, MUNW; metabolically healthy OWOB, MHO; and metabolically unhealthy OWOB, MUO. Unhealthy was defined as having ≥2 metabolic syndrome components. General linear models tested for differences in baseline and change in measures of body composition (fat mass [FM], fat-free mass [FFM], % body fat [%BF], visceral fat) after adjusting for age, sex, and ethnicity (and baseline value in change models). Results: Table 1 shows adjusted mean baseline and change in body composition values by group. Baseline body composition tended to track with weight status, with NW adults having lower FM, %BF, and visceral fat compared to obese adults (p&lt;0.05), regardless of metabolic health. However, the MHO group had lower baseline values of these traits compared to MUO (p&lt;0.05). Body composition measures significantly improved with exercise training in all groups, however, the magnitude of change differed between groups. For example, both NW groups had larger decreases in %BF compared to the obese groups, with MUNW showing the largest decrease. Conversely, MHNW showed the largest decrease in visceral fat, which was greater than both obese groups, but change in visceral fat was similar between MHO and MUNW. Conclusions: Normal weight adults tended to have better body composition profiles at baseline and larger improvements with exercise compared to obese adults, regardless of metabolic health. Within weight groups, body composition improved regardless of metabolic health status.

No abstract is provided for this article.

Age is associated with increased deposition of visceral adipose tissue. We examined whether this age-related change in regional adipose tissue distribution had an impact on low-density lipoprotein (LDL) particle size. For this purpose, the plasma lipoprotein-lipid profile, including LDL peak particle diameter as determined by gradient gel electrophoresis, was assessed in 38 young men (aged 26.4 ± 4.2 years, mean ± SD) and compared with 40 middle-aged men (55.9 ± 6.2 years). Middle-aged men had higher values for total body fat and visceral adipose tissue area as measured by computed tomography than young men (P < .001). Although significant differences were noted between the two age groups for plasma cholesterol, triglyceride (TG), apolipoprotein B (apo B), LDL cholesterol, and LDL apo B, as well as the cholesterol to high-density lipoprotein (HDL) cholesterol ratio (P < .001), no difference was found for LDL peak particle size between young and middle-aged men. While visceral adipose tissue was a significant correlate of plasma lipoprotein levels, the fasting TG concentration was the best predictor of LDL particle size, and the regression of TG levels on LDL peak particle diameter was not different between the two age groups. These results suggest that middle-aged men are characterized by an increased concentration of LDL particles (reflected by increased LDL apo B levels) but not by a reduced LDL peak particle size compared with young men. It is therefore proposed that in the absence of an important age-related change in TG levels, age per se is associated with an increased concentration of atherogenic LDL particles rather than a reduction of LDL particle diameter.

PURPOSE To evaluate gender specific differences in changes in macronutrient utilization at submaximal power outputs (PO) as a result of a supervised 20-wk aerobic exercise program in 733 sedentary individuals (312 males and 411 females) aged 17–65 yr participating in the HERITAGE Family Study. METHODS Cycle ergometer training was performed at four participating clinical centers, three times a week for 20 weeks. Intensity was initially set at a training heart rate (THR) equivalent to 55% VO2max for 30 min per session and progressed to a THR corresponding to 75% pre-training VO max for 50 min for the final 6 weeks. Metabolic data were collected after 3 minutes of relative steady state at a PO of 50W and at 60% VO2max. LIMITATIONS The HERITAGE exercise tests were not designed to address metabolic issues. Subjects undertook the exercise tests under variable conditions: No effort was made to standardize the diet or meal time prior to the tests and the exercise tests varied slightly to adjust for individual fitness. The pre-exercise conditions were heterogeneous among subjects and possibly varied from the pre- to post-training tests. Metabolic data were collected after 3 minutes of relative steady state at a PO of 50W and at 60% VO2max. RESULTS Overall, fat utilization, as a percentage of the total energy substrate, increased post-training at the fixed value of 50W (21.8 ±16% to 36.5 ±13%, P <0.01), and at the relative value of 60% of VO2max (11.3 ±13.6% to 21.9 ± 12.2%, P <0.01) even though watts at 60% of VO2max increased from 97.6 ± 27.5 to 121.9 ± 34.4W. Females increased fat utilization, as a percent of the total, more at 50Wthan did males (A=17.2% ±13% vs. A=11.5 ±13%, P <0.01) but were not different at 60% VO2max. CONCLUSIONS Aerobic exercise training in previously sedentary individuals increases fat as a substrate at fixed intensities of training as well as at moderate intensities relative to VO2max. Women increased fat oxidation at fixed intensities, as a percentage of total macronutrient utilization, more than did men. The large sample size and consistency of the data suggest that these results are valuable information for previously sedentary individuals in spite of the numerous limitations. These data show the benefits of aerobic training for improving fat oxidation due to exercise training. Sponsored by multiple grants by NHLBI.

In a case-control study, we examined the contribution of two genes that may play a role in discriminating highly trained endurance athletes (EA) from sedentary controls (SC). The EA group included 117 males recruited about equally in Canada and Germany on the basis that they had a ˙VO2max > 73ml/kg·min-1. The SC group comprised 114 unrelated sedentary males from the Québec Family Study who had estimated ˙VO2max values below 48 ml/kg·min-1. PCR and Southern-blotting techniques were used to detect mutations in TNFα and HSPA1 genes, both located on 6p21.3. The genotype distributions are presented in thetable. All distributions were in a Hardy-Weinberg equilibrium. No difference was found between EA and SC for the distribution of genotypes or allelic frequencies. Similarly, no difference was seen between the EA with ˙VO2max> 80 ml/kg·min-1 and the other EA or SC. In summary, we found no evidence that the specific mutations tested in these two candidate genes account for the difference in EA and SC status.

No abstract is provided for this article.