Peroxisome proliferator-activated receptor-delta polymorphisms are associated with physical performance and plasma lipids: the HERITAGE Family Study

We tested the hypothesis that peroxisome proliferator-activated receptor-delta (PPARdelta) gene polymorphisms are associated with cardiorespiratory fitness and plasma lipid responses to endurance training. Associations between the PPARdelta exon 4 +15 C/T and exon 7 +65 A/G polymorphisms and maximal exercise capacity and plasma lipid responses to 20 wk of endurance training were investigated in healthy white (n = 477) and black (n = 264) subjects. In black subjects, the exon 4 +15 C/C homozygotes showed a smaller training-induced increase in maximal oxygen consumption (P = 0.028) than the C/T and T/T genotypes. Similarly, a lower training response in maximal power output was observed in the exon 4 +15 C/C homozygotes (P = 0.005) compared with the heterozygotes and the T/T homozygotes in black subjects, and a similar trend was evident in white subjects (P = 0.087). In white subjects, baseline apolipoprotein A-1 (Apo A-1)levels were higher in the exon 4 +15 C/C (P = 0.011) and exon 7 +65 G/G (P = 0.05) genotypes compared with those in the other genotypes. In white subjects, exon 4 +15 C/C (P = 0.0025) and exon 7 +65 G/G (P = 0.011) genotypes showed significantly greater increases in plasma high-density lipoprotein-cholesterol (HDL-C) levels with endurance training than in the other genotypes, whereas in black subjects the exon 4 +15 CC homozygotes tended to increase (P = 0.057) their Apo A-1 levels more than the T allele carriers. DNA sequence variation in the PPARdelta locus is a potential modifier of changes in cardiorespiratory fitness and plasma HDL-C in healthy individuals in response to regular exercise.     

Interleukin-6 genotype is associated with high-density lipoprotein cholesterol responses to exercise training

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) and its subfractions are modifiable with exercise training and these responses are heritable. The interleukin-6 (IL6)-174G/C polymorphism may be associated with HDL-C levels. We hypothesized that the IL6-174G/C polymorphism would be associated with plasma HDL-C response to exercise training. METHODS AND RESULTS: Sixty-five 50- to 75-year-olds on a standardized diet were studied before and after 24 weeks of aerobic exercise training. Significant differences existed among genotype groups for change with exercise training in HDL-C, HDL3-C, integrated HDL4,5NMR-C, and HDLsize. The CC genotype group increased HDL-C more than the GG (7.0 +/- 1.3 v. 1.0 +/- 1.1 mg/dL, p = 0.001) and GC groups (3.3 +/- 0.9 mg/dL, p = 0.02); for HDL3-C, the CC group increased more than the GG (6.1 +/- 1.0 v. 0.9 +/- 0.9, mg/dL p < 0.001) and GC groups (2.5 +/- 0.7 mg/dL, p = 0.006). Integrated HDL4,5NMR-C increased more in the CC than GG group (6.5 +/- 1.6 mg/dL v. 1.0 +/- 1.3 mg/dL, p = 0.01), as did HDLsize compared to the GG (CC: 0.3 +/- 0.1 v. GG: 0.1 +/- 0.1 nm, p = 0.02) and GC (0.0 +/- 0.0 nm, p = 0.007) groups. CONCLUSIONS: IL6 genotype is associated with HDL-C response to exercise training.     

Lipid metabolism response to a single, prolonged bout of endurance exercise in healthy young men

To discover the alterations in lipid metabolism linked to postexercise hypotriglyceridemia, we measured lipid kinetics, lipoprotein subclass distribution and lipid transfer enzymes in seven healthy, lean, young men the day after 2 h of cycling and rest. Compared with rest, exercise increased fatty acid rate of appearance and whole body fatty acid oxidation by approximately 65 and 40%, respectively (P < 0.05); exercise had no effect on VLDL-triglyceride (TG) secretion rate, increased VLDL-TG plasma clearance rate by 40 +/- 8%, and reduced VLDL-TG mean residence time by approximately 40 min and VLDL-apolipoprotein B-100 (apoB-100) secretion rate by 24 +/- 8% (all P < 0.05). Exercise also reduced the number of VLDL but almost doubled the number of IDL particles in plasma (P < 0.05). Muscle lipoprotein lipase content was not different after exercise and rest, but plasma lipoprotein lipase concentration increased by approximately 20% after exercise (P < 0.05). Plasma hepatic lipase and lecithin:cholesterol acyltransferase concentrations were not affected by exercise, whereas cholesterol ester transfer protein concentration was approximately 10% lower after exercise than after rest (P = 0.052). We conclude that 1) greater fatty acid availability after exercise does not stimulate VLDL-TG secretion, probably because of the increase in fatty acid oxidation and possibly also fatty acid use for restoration of tissue TG stores; 2) reduced secretion of VLDL-apoB-100 lowers plasma VLDL particle concentration; and 3) increased VLDL-TG plasma clearance maintains low plasma TG concentration but is not accompanied by similar increases in subsequent steps of the delipidation cascade. Acutely, therefore, the cardioprotective lowering of plasma TG and VLDL concentrations by exercise is counteracted by a proatherogenic increase in IDL concentration.     

AGT M235T and ACE ID polymorphisms and exercise blood pressure in the HERITAGE Family Study

We investigated the association between angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) gene polymorphisms and exercise training responses of resting and exercise blood pressure (BP). BP at rest and during submaximal (50 watts) and maximal exercise tests was measured before and after 20 wk of endurance training in 476 sedentary normotensive Caucasian subjects from 99 families. AGT M235T and ACE insertion/deletion polymorphisms were typed with PCR-based methods. Men carrying the AGT MM and MT genotypes showed 3. 7 +/- 0.6 and 3.2 +/- 0.5 (SE) mmHg reductions, respectively, in diastolic BP at 50 watts (DBP(50)), whereas, in the TT homozygotes, the decrease was 0.4 +/- 1.0 mmHg (P = 0.016 for trend, adjusted for age, body mass index, and baseline DBP(50)). Men with the ACE DD genotype showed a slightly greater decrease in DBP(50) (4.4 +/- 0.6 mmHg) than the II and ID genotypes (2.8 +/- 0.7 and 2.4 +/- 0.5 mmHg, respectively, P = 0.050). Furthermore, a significant (P = 0.022) interaction effect between the AGT and ACE genes was noted for DBP(50); the AGT TT homozygotes carrying the ACE D allele showed no response to training. Men with the AGT TT genotype had greater (P = 0.007) diastolic BP (DBP) response to acute maximal exercise at baseline. However, the difference disappeared after the training period. No associations were found in women. These data suggest that, in men, the genetic variation in the AGT locus modifies the responsiveness of submaximal exercise DBP to endurance training, and interactions between the AGT and ACE loci can alter this response.     

Changes in cardiorespiratory fitness and coronary heart disease risk factors following 24 wk of moderate- or high-intensity exercise of equal energy cost.

This study was designed to investigate the effect of exercise intensity on cardiorespiratory fitness and coronary heart disease risk factors. Maximum oxygen consumption (Vo(2 max)), lipid, lipoprotein, and fibrinogen concentrations were measured in 64 previously sedentary men before random allocation to a nonexercise control group, a moderate-intensity exercise group (three 400-kcal sessions per week at 60% of Vo(2 max)), or a high-intensity exercise group (three 400-kcal sessions per week at 80% of Vo(2 max)). Subjects were instructed to maintain their normal dietary habits, and training heart rates were represcribed after monthly fitness tests. Forty-two men finished the study. After 24 wk, Vo(2 max) increased by 0.38 +/- 0.14 l/min in the moderate-intensity group and by 0.55 +/- 0.27 l/min in the high-intensity group. Repeated-measures analysis of variance identified a significant interaction between monthly Vo(2 max) score and exercise group (F = 3.37, P < 0.05), indicating that Vo(2 max) responded differently to moderate- and high-intensity exercise. Trend analysis showed that total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and fibrinogen concentrations changed favorably across control, moderate-intensity, and high-intensity groups. However, significant changes in total cholesterol (-0.55 +/- 0.81 mmol/l), low-density lipoprotein cholesterol (-0.52 +/- 0.80 mmol/l), and non-high-density lipoprotein cholesterol (-0.54 +/- 0.86 mmol/l) were only observed in the high-intensity group (all P < 0.05 vs. controls). These data suggest that high-intensity training is more effective in improving cardiorespiratory fitness than moderate-intensity training of equal energy cost. These data also suggest that changes in coronary heart disease risk factors are influenced by exercise intensity.     

Impact of adiponectin gene polymorphisms on plasma lipoprotein and adiponectin concentrations of viscerally obese men

The aim of this study was first to examine the relationships between adiponectin gene (Apm1) polymorphisms and anthropometric indices as well as plasma adiponectin and lipoprotein/lipid levels, and then to investigate whether the presence of visceral obesity or insulin resistance may modulate the impact of these polymorphisms on metabolic risk variables. Molecular screening of the Apm1 gene was achieved, and a sample of 270 unrelated men recruited from the greater Quebec City area and selected to cover a wide range of body fatness values was genotyped. Sequencing of the Apm1 gene revealed two previously reported polymorphisms (c.45T>G and c.276G>T) as well as two newly identified genetic variations (-13752delT and -13702G>C). Carriers of the c.276T allele had higher LDL-cholesterol and lower HDL-triglyceride concentrations than did 276G/G homozygotes (P=0.02 and P=0.01, respectively). Carriers of the c.45G allele exhibited higher plasma adiponectin concentrations than did 45T/T homozygotes (P=0.04). After dividing each genotype group into subgroups for visceral AT, homozygotes for the normal allele at position -13752delT, carriers of the c.45G allele, and carriers of the c.276T allele had similar total apolipoprotein B (apoB) concentrations, whether they were viscerally obese or not. These results suggest that some Apm1 gene polymorphisms influence plasma adiponectin concentrations and lipoprotein/lipid levels. In addition, the impact of these polymorphisms is modulated by the presence of visceral obesity.     

Habitual consumption of eggs does not alter the beneficial effects of endurance training on plasma lipids and lipoprotein metabolism in untrained men and women

Changes in plasma lipid and apolipoprotein profiles were evaluated in 12 healthy, unfit subjects (VO(2peak) 39.1+/-2.8 ml.kg(-1).min(-1); 5 women, 7 men) at baseline and following endurance exercise training. The exercise protocol consisted of a 6-week endurance exercise training program (4-5 days week(-1); 60 min.session(-1); > or =65% HR(max)). Subjects were randomly assigned to consume an egg- (n=6; 12 eggs.week(-1)) or no-egg (n=6; 0 eggs.week(-1))-based, eucaloric, standardized diet for 8 weeks. Both diets were macronutrient balanced [60% carbohydrate, 30% fat, 10% protein (0.8 g.kg(-1).day(-1))] and individually designed for weight maintenance. Plasma lipids were measured twice within the same week at baseline and following exercise training. At baseline, subjects were normolipidemic with values of 163.9+/-41.8, 84.8+/-36.7, 60.6+/-15.4 and 93.1+/-52 mg dl(-1) for total cholesterol, LDL cholesterol and HDL cholesterol and triglyceride concentrations, respectively. A two-way ANOVA was used to analyze diet and exercise effects and interactions. In both groups, endurance exercise training resulted in a significant 10% increase in HDL-C (P<.05), a 19% decrease in Apo B concentrations (P<.05) and reductions in plasma CETP activity (P<.05). Plasma LDL-C decreased by 21% (P=.06). No main effects of diet or interactions with plasma lipids or Apo B concentrations were observed. These data demonstrate that endurance training improved the plasma lipid profiles of previously unfit, normolipidemic subjects independent of dietary cholesterol intake from eggs.     

NADPH oxidase p22phox gene variants are associated with systemic oxidative stress biomarker responses to exercise training.

Systemic oxidative stress plays a role in many degenerative diseases. Although regular physical activity has been known as the most effective nonpharmacological intervention to alleviate the oxidative stress, the beneficial effect varies between individuals. We investigated whether NADPH oxidase p22phox gene C242T and A640G polymorphisms are associated with systemic oxidative stress level response to exercise training (ExTr). Fifty-nine sedentary middle-aged to older Caucasians with relatively high cardiovascular disease risk factors underwent a 6-mo standardized ExTr program. Body mass index, plasma lipoprotein-lipid profiles, cardiovascular fitness, and plasma thiobarbituric acid reactive substances (TBARS) were measured before and after ExTr. Demographic and initial levels of cardiovascular disease risk factors were similar among genotype groups for both polymorphisms. Overall, TBARS was decreased by 16% with ExTr in the entire group (P < 0.001). There was no significant difference in TBARS changes with ExTr among the C242T genotype groups. However, A allele carriers showed greater reduction in TBARS than noncarriers at the A640G locus (P = 0.05). There was a significant interaction (P = 0.05) between ExTr and A640G polymorphism in TBARS changes with ExTr. This interaction remained after accounting for age and baseline TBARS level. Furthermore, diplotype analysis showed that TBARS was decreased to a greater extent in the C242/A640 haplotype carriers compared with the noncarriers (P < 0.05). We found that p22phox polymorphisms, especially A640G, were associated with differential changes in systemic oxidative stress with aerobic exercise training.     

Hepatic lipase gene -514C>T variant is associated with exercise training-induced changes in VLDL and HDL by lipoprotein lipase

Our objective was to test the hypothesis that a common polymorphism in the hepatic lipase (HL) gene (LIPC -514C>T, rs1800588) influences aerobic exercise training-induced changes in TG, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) through genotype-specific increases in lipoprotein lipase (LPL) activity and that sex may affect these responses. Seventy-six sedentary overweight to obese men and women aged 50-75 yr at risk for coronary heart disease (CHD) underwent a 24-wk prospective study of the LIPC -514 genotype-specific effects of exercise training on lipoproteins measured enzymatically and by nuclear magnetic resonance, postheparin LPL and HL activities, body composition by dual energy x-ray absorptiometry and computer tomography scan, and aerobic capacity. CT genotype subjects had higher baseline total cholesterol, HDL-C, HDL(2)-C, large HDL, HDL particle size, and large LDL than CC homozygotes. Exercise training elicited genotype-specific decreases in VLDL-TG (-22 vs. +7%; P < 0.05; CC vs. CT, respectively), total VLDL and medium VLDL, and increases in HDL-C (7 vs. 4%; P < 0.03) and HDL(3)-C with significant genotype×sex interactions for the changes in HDL-C and HDL(3)-C (P values = 0.01-0.02). There were also genotype-specific changes in LPL (+23 vs. -6%; P < 0.05) and HL (+7 vs. -24%; P < 0.01) activities, with LPL increasing only in CC subjects (P < 0.006) and HL decreasing only in CT subjects (P < 0.007). Reductions in TG, VLDL-TG, large VLDL, and medium VLDL and increases in HDL(3)-C and small HDL particles correlated significantly with changes in LPL, but not HL, activity only in CC subjects. This suggests that the LIPC -514C>T variant significantly affects training-induced anti-atherogenic changes in VLDL-TG, VLDL particles, and HDL through an association with increased LPL activity in CC subjects, which could guide therapeutic strategies to reduce CHD risk.     

Aerobic exercise training reduces epicardial fat in obese men

The purpose of this study was to determine the effects of exercise training on ventricular epicardial fat thickness in obese men and to investigate the relationship of the change in epicardial fat thickness to changes in abdominal fat tissue following exercise training. Twenty-four obese middle-aged men [age, 49.4 +/- 9.6 yr; weight, 87.7 +/- 11.2 kg; body mass index (BMI), 30.7 +/- 3.3 kg/m(2); peak oxygen consumption, 28.4 +/- 7.2 ml.kg(-1).min(-1); means +/- SD] participated in this study. Each participant completed a 12-wk supervised exercise training program (60-70% of the maximal heart rate; 60 min/day, 3 days/wk) and underwent a transthoracic echocardiography. The epicardial fat thickness on the free wall of the right ventricle was measured from both parasternal long- and short-axis views. The visceral adipose tissue (VAT) and subcutaneous adipose tissues were measured by computed tomography. Following exercise training, the epicardial fat thickness was significantly decreased (P < 0.001). The percentage change of epicardial fat thickness was twice as high compared with those of waist, BMI, and body weight of original values (P <0.05). There was a significant relationship (r = 0.525, P = 0.008) between changes in the epicardial fat thickness and VAT with exercise training. Stepwise multiple regression analysis revealed that the change in VAT, change in systolic blood pressure, and change in quantitative insulin sensitivity check index were independently related to the change epicardial fat thickness (P < 0.05). The ventricular epicardial fat thickness is reduced significantly after aerobic exercise training and is associated with a decrease in VAT. These results suggest that aerobic exercise training may be an effective nonpharmacological strategy for decreasing the ventricular epicardial fat thickness and visceral fat area in obese middle-aged men.     

Acute vascular responses to isometric handgrip exercise and effects of training in persons medicated for hypertension

Previous work from our laboratory demonstrated that isometric handgrip (IHG) training improved local, endothelium-dependent vasodilation in medicated hypertensives [McGowan CL (PhD Thesis), 2006; McGowan et al. Physiologist 47: 285, 2004]. We investigated whether changes in the capacity of smooth muscle to dilate (regardless of endothelial factors) influenced this training-induced change, and we examined the acute vascular responses to a single bout of IHG. Seventeen subjects performed four 2-min unilateral IHG contractions at 30% of maximal voluntary effort, three times a week for 8 wk. Pre- and posttraining, brachial artery flow-mediated dilation (FMD, an index of endothelium-dependent vasodilation) and nitroglycerin-mediated maximal vasodilation (an index of endothelium-independent vasodilation) were measured in the exercised arm by using ultrasound before and immediately after acute IHG exercise. IHG training resulted in improved resting brachial FMD (P < 0.01) and no change in nitroglycerin-mediated maximal vasodilation. Pre- and posttraining, brachial artery FMD decreased following an acute bout of IHG exercise (normalized to peak shear rate, pre-, before IHG exercise: 0.01 +/- 0.002, after IHG exercise: 0.008 +/- 0.002%/s(-1); post-, before IHG exercise: 0.020 +/- 0.003, after IHG exercise: 0.010 +/- 0.003%/s(-1); P < 0.01). Posttraining, resting brachial artery FMD improved yet nitroglycerin-mediated maximal vasodilation was unchanged in persons medicated for hypertension. This suggests that the training-induced improvements in the resting brachial artery FMD were not due to underlying changes in the forearm vasculature. Acute IHG exercise attenuated brachial artery FMD, and although this impairment may be interpreted as hazardous to medicated hypertensives with already dysfunctional endothelium, the effects appear transient as repeated exposure to the IHG stimulus improved resting endothelium-dependent vasodilation.     

Aerobic training improves exercise-induced lipolysis in SCAT and lipid utilization in overweight men

The aim of this study was to investigate whether endurance training improves lipid mobilization and oxidation in overweight subjects. Eleven young men (25.6 +/- 1.4 yr and body mass index 27.7 +/- 0.2) performed a 4-mo training program consisting of practicing aerobic exercise 5 days/wk. Before and after the training period, lipid oxidation was explored during a 60-min exercise at 50% of peak O2 consumption by use of indirect calorimetry. Lipid mobilization and antilipolytic alpha2-adrenoceptor effect were also studied using the microdialysis method in abdominal subcutaneous adipose tissue (SCAT). After training, plasma nonesterified fatty acid (NEFA) levels, at rest and during exercise, were significantly lower than before (P < 0.001). Lipolysis in SCAT was significantly higher after than before training. An antilipolytic alpha2-adrenoceptor effect in SCAT was underlined during exercise before training and disappeared after. The respiratory exchange ratio was lower after training, i.e., the percentage of lipid oxidation was higher only at rest. The amount of lipid oxidized was higher after training, at rest, and during exercise. Although exercise power was higher after training, the relative intensity was equivalent, as suggested by a similar increase in plasma catecholamine concentrations before and after training. In conclusion, 4-mo training in overweight men improved lipid mobilization through a decrease of antilipolytic alpha2-adrenoceptor effect in SCAT and lipid oxidation during moderate exercise. Training induced a decrease of blood NEFA, predicting better prevention of obesity.     

Impaired substrate oxidation in healthy elderly men after eccentric exercise.

The metabolic response to eccentric exercise in healthy older adults is unknown. Therefore, substrate metabolism was examined in the basal state and after sustained hyperglycemia (180 min, 10 mM) in eight healthy, sedentary older [66 +/- 2 yr; body mass index (BMI) of 25.5 +/- 1.2 kg/m] and nine younger (23 +/- 1 yr; BMI of 23.6 +/- 1.7 kg/m) men, under control conditions and 48 h after eccentric exercise. Indirect calorimetry was performed to evaluate carbohydrate and lipid oxidation (C(ox) and L(ox), respectively). Eccentric exercise caused muscle soreness and increased plasma creatine kinase in both groups of men (P < 0.02). Although a similar level of hyperglycemia was maintained in the two groups, glucose infusion rates were lower (P < 0.001) in the older men. Compared with basal levels, hyperglycemia stimulated an increase in C(ox) and a decrease in L(ox) during the control and exercise trials in the younger group (P < 0.03), but only during the control trial in the older subjects (P < 0.007). C(ox) was unchanged after eccentric exercise in the younger men [4.00 +/- 0.30 vs. 3.54 +/- 0.44 mg x kg fat-free mass (FFM)(-1) x min(-1); exercise vs. control] but was suppressed by 20% in the older group (3.37 +/- 0.37 vs. 4.21 +/- 0.23 mg x kg FFM(-1) x min(-1); P < 0.04). Moreover, L(ox) was reduced by 38% in the younger subjects (0.47 +/- 0.09 vs. 0.76 +/- 0.10 mg x kg FFM(-1) x min(-1); P< 0.03) but was augmented by 89% in the older group (0.68 +/- 0.11 vs. 0.36 +/- 0.08 mg x kg FFM(-1) x min(-1); P < 0.04). In addition, hyperglycemia-stimulated C(ox), L(ox), and respiratory exchange ratio responses to eccentric exercise were related to abdominal adiposity (r = -0.57, P < 0.04, r = 0.68, P < 0.02 and r = -0.60, P < 0.02, respectively). Despite normal glucose tolerance and the absence of obesity per se, older men experience a reduction in carbohydrate oxidation in response to hyperglycemia after eccentric exercise.     

Influence of the interleukin-6 -174 G/C gene polymorphism on exercise training-induced changes in glucose tolerance indexes.

A polymorphism in the IL-6 gene, a G-to-C substitution 176 bp upstream of the ATG translation initiation site, has been associated with diabetes prevalence and insulin resistance. Interventions including exercise training are frequently used to modify cardiovascular disease risk factors. Consequently, this project examined associations between the IL-6 -174 genotype and oral glucose tolerance test outcomes in 50- to 75-yr-old sedentary men and postmenopausal women before and after aerobic exercise training. Among the 87 individuals who started the study, 56 were retested after 6 mo of aerobic exercise training. Subject characteristics at baseline did not differ between the IL-6 genotype groups with the exception of fasting glucose, which was higher (P = 0.02, covariates age, gender, and ethnicity) in the CC genotype group. The training-induced change in glucose area under the curve during the oral glucose tolerance test varied between the IL-6 -174 genotype groups (P = 0.05, covariates age, gender, ethnicity, baseline glucose area under the curve, and percent body fat change) with a significant decrease occurring only in the GG genotype group. Insulin outcomes did not differ among the groups at baseline or after training. Training-induced changes in weight, percent body fat, maximal oxygen consumption, fasting glucose, and an insulin sensitivity index also changed similarly among the genotype groups. In conclusion, fasting glucose and the extent to which glucose tolerance changes with exercise training may be influenced by the IL-6 -174 gene polymorphism.     

Common sequence variations in ABCG8 are related to plant sterol metabolism in healthy volunteers

Polymorphisms in the ATP binding cassette (ABC) transporters ABCG5 and ABCG8 are related to plasma plant sterol concentrations. It is not known whether these polymorphisms are also associated with variations in serum plant sterol concentrations during interventions affecting plant sterol metabolism. We therefore decided to study changes in serum plant sterol concentrations with ABCG5/G8 polymorphisms after consumption of plant stanol esters, which decrease plasma plant sterol concentrations. Cholesterol-standardized serum campesterol and sitosterol concentrations were significantly associated with the ABCG8 T400K genotype, as were changes in serum plant sterol concentrations after consumption of plant stanols. The reduction of -57.1 +/- 38.3 10(2) x micromol/mmol cholesterol for sitosterol in TT subjects was significantly greater compared with the -36.0 +/- 18.7 reduction in subjects with the TK genotype (P = 0.021) and the -16.9 +/- 13.0 reduction in subjects with the KK genotype (P = 0.047). Changes in serum campesterol concentrations showed a comparable association. No association with serum LDL cholesterol was found. Genetic variation in ABCG8 not only explains cross-sectional differences in serum plant sterol concentrations but also determines a subject's responsiveness to changes in serum plant sterols during interventions known to affect plant sterol metabolism.     

High-intensity interval aerobic training reduces hepatic very low-density lipoprotein-triglyceride secretion rate in men

A single bout of strenuous endurance exercise reduces fasting plasma triglyceride (TG) concentrations the next day (12-24 h later) by augmenting the efficiency of very low-density lipoprotein (VLDL)-TG removal from the circulation. Although much of the hypotriglyceridemia associated with training is attributed to the last bout of exercise, the relevant changes in VLDL-TG metabolism have never been investigated. We therefore examined basal VLDL-TG kinetics in a group of sedentary young men (n=7) who underwent 2 mo of supervised high-intensity interval training (3 sessions/wk; running at 60 and 90% of peak oxygen consumption in 4-min intervals for a total of 32 min; gross energy expenditure: 446+/-29 kcal) and a nonexercising control group (n=8). Each subject completed two stable isotope-labeled tracer infusion studies in the postabsorptive state, once before and again after the intervention (approximately 48 h after the last exercise bout in the training group). Peak oxygen consumption increased by approximately 18% after training (P 0.7) in VLDL-TG plasma clearance rate and the mean residence time of VLDL-TG in the circulation. No significant changes in VLDL-TG concentration and kinetics were observed in the nonexercising control group (all P >or= 0.3). We conclude that a short period of high-intensity interval aerobic training lowers the rate of VLDL-TG secretion by the liver in previously sedentary men. This is different from the mechanism underlying the hypotriglyceridemia of acute exercise; however, it remains to be established whether our finding reflects an effect of the longer time lapse from the last exercise bout, an effect specific to the type of exercise performed, or an effect of aerobic training itself.     

Postprandial triglyceride levels in familial combined hyperlipidemia. The role of apolipoprotein E and lipoprotein lipase polymorphisms

The effect of apolipoprotein E genotype and polymorphisms of lipoprotein lipase gene on plasma postprandial triglyceride levels in familial combined hyperlipidemic subjects and their relatives have not been sufficiently studied. This study included sixteen familial combined hyperlipidemic parents (G1): age: 52 +/- 9 years with total-cholesterol: 7.2 +/- 1.7 mmol/L, fasting triglycerides: 2.8 +/- 1.4 mmol/L and sixteen children (G2) (twelve were normolipidemic): of age: 22 +/- 5 years with total-cholesterol: 5.2 +/- 1.1 mmol/L, fasting triglycerides: 2.06 +/- 1.8 mmol/L and twelve normolipidemic, healthy controls. Blood samples were taken fasting and 2, 4, 6, 8, 10 hr postprandially after the standard fat rich test meal. We determined lipid parameters, apolipoprotein E and lipoprotein lipase HindIII and PvuII polymorphisms as well. The 6-hr critical postprandial triglyceride values were abnormal in both G1: 5.88 +/- 2.7 mmol/L and G2: 3.53 +/- 2.7 mmol/L (p <0.001), respectively, and differed significantly (p <0.001) from each other. The subjects of familial combined hyperlipidemic families with E4 allele in both generations exhibited significantly (p <0.001) higher and extended postprandial lipemia. We did not find significant effects of lipoprotein lipase HindIII or PvuII polymorphisms on the fasting lipid values alone, however in normolipidemic subjects from the same families the homozygosity of HindIII variation was associated with higher triglyceride postprandial peak (p <0.01). The main findings of our study are that i.) normolipidemic G2 subjects in familial combined hyperlipidemic families have already abnormal postprandial status, and ii.) the 6 h postprandial triglyceride values were correlated with fasting triglyceride levels, which showed association with the apolipoprotein E4 allele.     

Endurance training decreases plasma glucose turnover and oxidation during moderate-intensity exercise in men

To assess the effects of endurance training on plasma glucose kinetics during moderate-intensity exercise in men, seven men were studied before and after 12 wk of strenuous exercise training (3 days/wk running, 3 days/wk cycling). After priming of the glucose and bicarbonate pools, [U-13C] glucose was infused continuously during 2 h of cycle ergometer exercise at 60% of pretraining peak O2 uptake (VO2) to determine glucose turnover and oxidation. Training increased cycle ergometer peak VO2 by 23% and decreased the respiratory exchange ratio during the final 30 min of exercise from 0.89 +/- 0.01 to 0.85 +/- 0.01 (SE) (P less than 0.001). Plasma glucose turnover during exercise decreased from 44.6 +/- 3.5 mumol.kg fat-free mass (FFM)-1.min-1 before training to 31.5 +/- 4.3 after training (P less than 0.001), whereas plasma glucose clearance (i.e., rate of disappearance/plasma glucose concentration) fell from 9.5 +/- 0.6 to 6.4 +/- 0.8 ml.kg FFM-1.min-1 (P less than 0.001). Oxidation of plasma-derived glucose, which accounted for approximately 90% of plasma glucose disappearance in both the untrained and trained states, decreased from 41.1 +/- 3.4 mumol.kg FFM-1.min-1 before training to 27.7 +/- 4.8 after training (P less than 0.001). This decrease could account for roughly one-half of the total reduction in the amount of carbohydrate utilized during the final 30 min of exercise in the trained compared with the untrained state.     

Evidence of LPL gene-exercise interaction for body fat and LPL activity: the HERITAGE Family Study.

Evidence of a gene-exercise interaction for traits related to body composition is limited. Here, the association between the lipoprotein lipase (LPL) S447X polymorphism and changes in body mass index, fat mass, percent body fat, abdominal visceral fat measured by computed tomography, and post-heparin plasma LPL activity in response to 20 wk of endurance training was investigated in 741 adult white and black subjects. Changes were compared between carriers and noncarriers of the X447 allele after adjustment for the effects of age and pretraining values. No evidence of association was observed in men. However, white women carrying the X447 allele exhibited greater reductions of body mass index (P = 0.01), fat mass (P = 0.01), and percent body fat (P = 0.03); in black women, the carriers exhibited a greater reduction of abdominal visceral fat (P = 0.05) and a greater increase in post-heparin LPL activity (P = 0.02). These results suggest that the LPL S447X polymorphism influences the training-induced changes in body fat and post-heparin LPL activity in women but not in men.     

Exercise training prevents decline in stroke volume during exercise in young healthy subjects.

Stroke volume (SV) increases above the resting level during exercise and then declines at higher intensities of exercise in sedentary subjects. The purpose of this study was to determine whether an attenuation of the decline in SV at higher exercise intensities contributes to the increase in maximal cardiac output (Qmax) that occurs in response to endurance training. We studied six men and six women, 25 +/- 1 (SE) yr old, before and after 12 wk of endurance training (3 days/wk running for 40 min, 3 days/wk interval training). Cardiac output was measured at rest and during exercise at 50 and 100% of maximal O2 uptake (Vo2max) by the C2H2-rebreathing method. VO2max was increased by 19% (from 2.7 +/- 0.2 to 3.2 +/- 0.3 l/min, P less than 0.001) in response to the training program. Qmax was increased by 12% (from 18.1 +/- 1 to 20.2 +/- 1 l/min, P less than 0.01), SV at maximal exercise was increased by 16% (from 97 +/- 6 to 113 +/- 8 ml/beat, P less than 0.001) and maximal heart rate was decreased by 3% (from 185 +/- 2 to 180 +/- 2 beats/min, P less than 0.01) after training. The calculated arteriovenous O2 content difference at maximal exercise was increased by 7% (14.4 +/- 0.4 to 15.4 +/- 0.4 ml O2/100 ml blood) after training. Before training, SV at VO2max was 9% lower than during exercise at 50% VO2max (P less than 0.05). In contrast, after training, the decline in SV between 50 and 100% VO2max was only 2% (P = NS). Furthermore, SV was significantly higher (P less than 0.01) at 50% VO2max after training than it was before. Left ventricular hypertrophy was evident, as determined by two-dimensional echocardiography at the completion of training. The results indicate that in young healthy subjects the training-induced increase in Qmax is due in part to attenuation of the decrease in SV as exercise intensity is increased.