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No abstract is provided for this article.

Metabolic responses to exercise training are variable. Metabolite profiling may aid in the clinical assessment of an individual's responsiveness to exercise interventions.To investigate the association between a novel circulating biomarker of hepatic fat, dimethylguanidino valeric acid (DMGV), and metabolic health traits before and after 20 weeks of endurance exercise training.This study involved cross-sectional and longitudinal analyses of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, a 20-week, single-arm endurance exercise clinical trial performed in multiple centers between 1993 and 1997. White participants with sedentary lifestyles who were free of cardiometabolic disease were included. Metabolomic tests were performed using a liquid chromatography, tandem mass spectrometry method on plasma samples collected before and after exercise training in the HERITAGE study. Metabolomics and data analysis were performed from August 2017 to May 2018.Plasma DMGV levels.The association between DMGV levels and measures of body composition, plasma lipids, insulin, and glucose homeostasis before and after exercise training.Among the 439 participants included in analyses from HERITAGE, the mean (SD) age was 36 (15) years, 228 (51.9%) were female, and the median (interquartile range) body mass index was 25 (22-28). Baseline levels of DMGV were positively associated with body fat percentage, abdominal visceral fat, very low-density lipoprotein cholesterol, and triglycerides, and inversely associated with insulin sensitivity, low-density lipoprotein cholesterol, high-density lipoprotein size, and high-density lipoprotein cholesterol (range of β coefficients, 0.17-0.46 [SEs, 0.026-0.050]; all P < .001, after adjusting for age and sex). After adjusting for age, sex, and baseline traits, baseline DMGV levels were positively associated with changes in small high-density lipoprotein particles (β, 0.14 [95% CI, 0.05-0.23]) and inversely associated with changes in medium and total high-density lipoprotein particles (β, -0.15 [95% CI, -0.24 to -0.05] and -0.19 [95% CI, -0.28 to -0.10], respectively), apolipoprotein A1 (β, -0.14 [95% CI, -0.23 to -0.05]), and insulin sensitivity (β, -0.13; P = 3.0 × 10-3) after exercise training.Dimethylguanidino valeric acid is an early marker of cardiometabolic dysfunction that is associated with attenuated improvements in lipid traits and insulin sensitivity after exercise training. Levels of DMGV may identify individuals who require additional therapies beyond guideline-directed exercise to improve their metabolic health.

No abstract is provided for this article.

The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268).All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents.The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

The purpose of this study was to examine ethnic differences in adiposity as measured by sum of skinfolds (SKF) and waist circumference (WC) in children and adolescents, after statistical adjustment for the BMI and age. A cross sectional sample of 3,218 (55% white, 49% male) children and adolescents aged 5-18 years who participated in the Bogalusa Heart Study (1992-1994) were included in these analyses. Sex-specific ANOVAs, adjusted for BMI and age, for each 2-year age group compared measures of adiposity (SKF and WC) between ethnic groups. No significant differences in the proportions of children and adolescents who were overweight and obese by ethnicity or sex were found. Mean SKF in normal weight (P < 0.0001) and overweight (P < 0.0001) categories was higher for white than black children of both sexes. Across most age categories, white boys and girls had significantly higher SKF than black boys and girls, respectively (P <or= 0.05). Across most age categories, white boys had significantly higher WC than black boys (P <or= 0.05) with no difference in the girls, when adjusted for BMI and age. Measures of adiposity in childhood and adolescence were significantly higher in white children compared to black children, when adjusted for BMI and age. Throughout childhood and adolescence, white boys and girls had higher SKF and white boys had higher WC. Differences in adiposity between ethnic groups should be considered in disease risk assessment and stratification as they are observed even for a given BMI level.

—Endothelium-dependent vasodilation is a mechanism that may affect blood pressure response to endurance training. Because NO plays a central role in this process, the endothelial NO synthase gene is a good candidate for the regulation of exercise blood pressure. We investigated the associations between an endothelial NO synthase gene polymorphism (Glu298Asp) and endurance training–induced changes in resting and submaximal exercise blood pressure in 471 white subjects of the HERITAGE Family Study. Two submaximal exercise tests at 50 W were conducted both before and after a 20-week endurance training program. Steady-state exercise blood pressure was measured twice in each test with an automated unit. The Glu298Asp polymorphism was typed with a PCR-based method and digestion with Ban II. Both systolic and diastolic blood pressure at 50 W decreased in response to the training program, whereas resting blood pressure remained unchanged. The decrease in diastolic blood pressure at 50 W was greater ( P =0.0005, adjusted for age, gender, baseline body mass index, and baseline diastolic blood pressure at 50 W) in the Glu/Glu homozygotes (4.4 [SEM 0.4] mm Hg, n=187) than in the heterozygotes (3.1 [0.4] mm Hg, n=213) and the Asp/Asp homozygotes (1.3 [0.7] mm Hg, n=71). The genotype accounted for 2.3% of the variance in diastolic blood pressure at 50 W training response. Both the Glu298 homozygotes and the heterozygotes had a greater ( P =0.013) training-induced reduction in rate-pressure product at 50 W than the Asp298 homozygotes. These data suggest that DNA sequence variation in the endothelial NO synthase gene locus is associated with the endurance training–induced decreases in submaximal exercise diastolic blood pressure and rate-pressure product in sedentary normotensive white subjects.

Cardiovascular variables have traditionally been scaled relative to body surface area (BSA, ratio scaling) to eliminate the effects of body size. The appropriateness of this scaling method has been questioned (Turley & Wilmore, Med. Sci. Sports Exerc., 30:S242, 1998). Allometric scaling is a newer technique to normalize data. PURPOSE: Determine the most appropriate method of scaling submaximal cardiovascular variables. METHODS: Cardiac output (Q) and stroke volume (SV) were measured at absolute (50 W) and relative (60% VO2max) power outputs on a cycle ergometer in 422 women and 337 men ages 17–65. BSA values ranged from 1.28–2.74. The allometric exponent b was determined from the equation Y=aXb (Y=SV or Q, X=BSA, and a = constant). RESULTS: Values of b for Q (0.36 and 0.71) and SV (0.80 and 0.93) at 50 W and 60% VO2max, respectively, were significantly different (p ≤ 0.05) from 1.00 (the value necessary if ratio scaling truly normalizes the physiological value) except for SV at 60%. Further, the scaled physiological values (Y/BSA1.00 and Y/BSAb) were correlated to BSA. The Pearson Product Moment Correlation coefficients were as follows: If properly normalized the physiological value (Y/X1.00 or Y/Xb) should be devoid of a relationship (r = 0.00) with the scaling value (BSA). CONCLUSION: Traditional ratio scaling does not truly normalize cardiovascular variables in this large data set. Determining the appropriate exponent b from the equation Y=aXb is a more appropriate method of scaling submaximal cardiovascular values.Table: No Caption Available

No abstract is provided for this article.

Body fatness, plasma lipids, lipoproteins, indicators of glucose metabolism, and resting as well as submaximal treadmill exercise systolic blood pressures (BPs) were measured in a sample of 25 normotensive obese premenopausal women. No association was observed between body fatness, risk factors for cardiovascular disease, and resting BP. However, body fatness and plasma cholesterol, low-density lipoprotein cholesterol (LDL-CHOL), LDL apolipoprotein B (apo B), and apo B concentrations, as well as the high-density lipoprotein cholesterol to cholesterol (HDL-CHOL/CHOL) ratio, showed significant correlations with systolic BP measured during submaximal exercise. In addition, fasting plasma insulin concentrations and the glucose and insulin areas under the oral glucose tolerance test (OGTT) curve were both significantly associated with systolic BP during submaximal exercise. Partial correlation analyses revealed that the associations between submaximal exercise systolic BP and plasma apo B and LDL apo B levels were in part independent from the level of obesity. These results indicate that plasma concentrations of lipoproteins and insulin are important correlates of the systolic BP during submaximal exercise in obese premenopausal women. Further analyses performed on two subgroups indicated that women with high exercise systolic BP values exhibited significant differences in their metabolic profile in comparison to women with low BP during exercise. These results suggest that the absolute systolic BP recorded during submaximal exercise may be useful in the early detection of individuals at risk for the development of cardiovascular disease in resting normotensive obese women.

Although many novel gene-metabolite and gene-protein associations have been identified using high-throughput biochemical profiling, systematic studies that leverage human genetics to illuminate causal relationships between circulating proteins and metabolites are lacking. Here, we performed protein-metabolite association studies in 3,626 plasma samples from three human cohorts. We detected 171,800 significant protein-metabolite pairwise correlations between 1,265 proteins and 365 metabolites, including established relationships in metabolic and signaling pathways such as the protein thyroxine-binding globulin and the metabolite thyroxine, as well as thousands of new findings. In Mendelian randomization (MR) analyses, we identified putative causal protein-to-metabolite associations. We experimentally validated top MR associations in proof-of-concept plasma metabolomics studies in three murine knockout strains of key protein regulators. These analyses identified previously unrecognized associations between bioactive proteins and metabolites in human plasma. We provide publicly available data to be leveraged for studies in human metabolism and disease.