Effect of Habitual Aerobic Exercise on Body Weight and Arterial Function in Overweight and Obese Men

Article Outline

• Abstract
• Methods
• Results
• Discussion
• References
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The effect of habitual exercise on vascular function, including central arterial distensibility and endothelial function, in obese subjects has not yet been clarified. We investigated whether aerobic exercise training affects central arterial distensibility and endothelial function in middle-age overweight and obese men. A total of 21 overweight and obese men (age 50 ± 2 years, body mass index 30 ± 1 kg/m²) completed a 12-week aerobic exercise intervention. Aerobic exercise training significantly reduced their body weight and resulted in a significant decrease in body mass index. After the weight-reduction exercise program, carotid arterial compliance (determined by simultaneous B-mode ultrasonography and arterial applanation tonometry on the common carotid artery) significantly increased; and the β-stiffness index, an index of arterial compliance adjusted for distending pressure, significantly decreased. The concentrations of plasma endothelin-1, a potent vasoconstrictor peptide produced by vascular endothelial cells, significantly decreased and plasma nitric oxide (measured as the stable end product [nitrite/nitrate]), a potent vasodilator produced by vascular endothelial cells, significantly increased after the weight-reduction exercise program. In conclusion, weight reduction by aerobic exercise training in overweight and obese men increased the central arterial distensibility. This increase might contribute to the improvement in endothelial function, as assessed by a decrease in endothelin-1 and an increase in nitric oxide, after exercise training-induced weight loss.

The prevalence of obesity in middle-age humans is increasing worldwide.¹, ² Obesity has been identified as an independent risk factor for cardiovascular morbidity and mortality.³, ⁴ It has been well established that regular aerobic exercise is an important strategy for preventing cardiovascular disease.⁵, ⁶, ⁷ However, the effects of aerobic exercise training on vascular function (i.e., central arterial distensibility and endothelial function) in overweight and obese adults are not known. Accordingly, the major aim of the present study was to examine whether aerobic exercise training affects central arterial distensibility in middle-age overweight and obese men and, if so, whether endothelial function, as assessed by endothelin-1 (ET-1) and nitric oxide (NO) concentrations, participates in the mechanism underlying the adaptation of central arterial distensibility to exercise training. We hypothesized that aerobic exercise training could induce weight reduction and an increase in central arterial distensibility in overweight and obese men, and that ET-1 and NO participate in the mechanism underlying this adaptation of central arterial distensibility to weight loss. To examine our hypothesis, we measured carotid arterial compliance; the β-stiffness index, an index of arterial compliance adjusted for distending pressure; and plasma ET-1 and NO concentrations before and after a 12-week aerobic exercise intervention program in middle-age overweight and obese men.

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Methods 

A total of 21 middle-age overweight and obese men participated in the present study. Candidates who were current smokers or who were taking any medications were excluded. None of the men had apparent cardiovascular disease, as assessed by medical history and physical examination. The overweight and obese groups were defined on the basis of the body mass index (BMI) (overweight group, BMI 25 to <30 kg/m² and obese group, BMI, ≥30 kg/m²). The institutional review board at the University of Tsukuba reviewed and approved the present study. All potential risks and procedures of the study were explained to the subjects, who provided written informed consent to participate in the study.

All overweight and obese men were studied before and after a 12-week training program. The participants were instructed to maintain current eating behaviors for the duration of the 12-week intervention. Dietary intake was assessed by 3-day weighed dietary records and dietary recall interviews for each participant at baseline and at the beginning of week 10 of the intervention by a skilled dietician. All measurements (excluding maximal oxygen uptake) were obtained between 8 am and 12 pm after abstinence from caffeine and an overnight fast. The men were studied at rest in the supine position in a quiet, temperature-controlled room (24° to 26°C). All measurements were performed after a resting period of ≥20 minutes.

The men performed exercise training in the form of walking and jogging, for sessions of 40 to 60 minutes each (3 days/wk). The men were supervised by 2 or 3 physical trainers. In the first 2 months, the exercise consisted only of walking, with the target Borg's scale ranging from 11 (light) to 13 (fairly hard). The distance walked was 3.5 and 4.5 km in the first and second months, respectively. In the last month, the men performed a combination of a 3.0-km brisk walk and a 1.0-km mid-intensity jog, with the target Borg's scale ranging from 13 (fairly hard) to 15 (hard). The men measured their heart rate using portable heart rate monitors (s610i, Polar Electro OY, Oulu, Finland) while walking and jogging and recorded the duration (in min) and intensity (heart rate or the Borg's scale) during each exercise session.

The maximal oxygen uptake was determined during a graded exercise test using a cycling ergometer (818E, Monark, Stockholm, Sweden). After a 2-minute warm up in 30 W, the subject started with a workload of 15 W each minute until volitional exhaustion occurred. Pulmonary ventilation and gas exchange were measured, breath-by-breath, with an on-line data acquisition system (Oxycon Alpha System, Mijnhardt, Breda, The Netherlands). The measurements of individual maximal oxygen uptake were obtained between 8 am and 2 pm.

Dual energy X-ray absorptiometry (DPX-L, Lunar, Madison, Wisconsin) was used to evaluate the segmental body composition, consisting of the fat mass and fat-free mass. Transverse scans were used to measure the fat mass and fat-free mass, and pixels of soft tissue were used to calculate the ratio of mass attenuation coefficients at 40 to 50 keV (low energy) and 80 to 100 keV (high energy), using software version 1.3Z (DPX-L, Lunar, Madison, Wisconsin).

The visceral fat area and subcutaneous fat area were measured using computed tomography (Somatom AR.C, Siemens, Erlangen, Germany), as previously described.⁸ The visceral and subcutaneous fat areas were calculated using a computer software program (FatScan, N2 System, Osaka, Japan).

The supine systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate were recorded from the left arm using a semiautomated device (Dinamap, Johnson & Johnson, New Jersey).

The combination of ultrasound imaging of the common carotid artery with the simultaneous applanation of tonometrically obtained arterial pressure from the contralateral carotid artery permitted the noninvasive determination of dynamic arterial compliance. The men were studied in quiet, at rest conditions while in the supine position. The common carotid artery diameter was measured from the images derived from an ultrasound machine (EnVisor, Koninklijke Philips Electronics, Eindhoven, The Netherlands) equipped with a high-resolution (7.5-MHz) linear-array transducer. Longitudinal images of the cephalic portion of the common carotid artery were acquired 1 to 2 cm proximal to the carotid bulb, with the transducer placed at a 90° angle to the vessel such that the near and far wall interfaces were clearly discernible. These images were recorded on a computer recorder, for later off-line analysis. The computer images were analyzed using image analysis software. All image analyses were performed by the same investigator. The points that corresponded to the maximum systolic expansion of the carotid artery and basal (minimum) diastolic relaxation were selected. The distances (or diameter) between the vessel far-wall and near-wall boundary, corresponding to the interface of the adventitia and media, were then measured.

Cross-sectional compliance⁹ was calculated from the change in the cross-sectional area (dA) and local pulse pressure (dP), using the formula cross-sectional compliance = dA/dP. dA was calculated as dA = π × ([D + dD]/2)² − π × (D/2).² The pressure wave forms of the left common carotid artery were recorded with an applanation tonometry device (formPWV/ABI, Colin Medical Technology, Komaki, Japan) and calibrated by equating the carotid mean arterial and diastolic blood pressure to that of the brachial artery.¹⁰

The β-stiffness index¹¹ was calculated using the equation β = ln (Ps/ Pd)/([Ds − Dd]/Dd), where Ds and Dd are the maximum and minimum arterial diameter and Ps and Pd are the highest and lowest blood pressure, respectively.¹⁰

Each blood sample was placed in a chilled tube containing aprotinin (300 kallikrein-inactivating U/ml) and ethylenediaminetetraacetic acid (2 mg/ml) and then centrifuged at 2,000g for 15 minutes at 4°C. The plasma was stored at −80°C until assayed. Plasma concentrations of ET-1 were determined using a sandwich-EIA Kit (Immuno-Biological Laboratories, Fujioka, Japan). The ET-1 assay was performed as previously described in our laboratory guidelines.⁷ The plasma NO level (measured as the concentration of its stable end-product, nitrite/nitrate [NO_x]) was determined using the methods followed in our laboratory.⁶ The serum concentrations of cholesterol and triglycerides and the plasma concentrations of glucose were determined using standard enzymatic techniques.

The data are expressed as the mean ± SE. To evaluate the differences in the levels before and after the weight reduction program, the Student's t test for paired values was used. The blood pressure-independent effect of weight loss on the β-stiffness index was tested using analysis of covariance. Analyses were performed using the Statistical Package for Social Sciences, version 16.0, for Windows, and p <0.05 was accepted as significant.

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Results 

No difference was found between the baseline and follow-up data for dietary intake (2,221 ± 90 vs 2,163 ± 106 kcal/day; p = NS). Table 1 lists the characteristics of each of the overweight and obese men (age 50 ± 2 years; BMI, 30 ± 1 kg/m²) before and after the 12-week exercise training-induced weight reduction program. The body weight; BMI; fat mass; body fat areas; serum concentrations of total cholesterol, LDL cholesterol, and triglycerides; systolic blood pressure; diastolic blood pressure; mean arterial pressure; pulse pressure, and heart rate significantly decreased after the intervention. The maximum oxygen uptake significantly increased after the exercise intervention (Figure 1). The arterial compliance significantly increased, and the β-stiffness index significantly decreased, after the exercise training-induced weight reduction program (Figure 2). Moreover, analysis of covariance revealed that the effect of the exercise intervention on the β-stiffness index was statistically independent of age, systolic blood pressure, diastolic blood pressure, and mean blood pressure (F = 1.6 and p <0.05). Thus, weight reduction by aerobic exercise in overweight and obese men increased central arterial distensibility. The plasma ET-1 concentration significantly decreased after the exercise training-induced weight reduction program (Figure 3). The plasma concentration of NO_x significantly increased with exercise training-induced weight loss (Figure 3).

Table 1. Individual characteristics of overweight and obese men before and after aerobic exercise-induced weight reduction program

BMI = body mass index; DBP = diastolic blood pressure; FBG = fasting blood glucose; FM = fat mass; HDL-C = high-density lipoprotein cholesterol; HR = heart rate; LDL-C = low-density lipoprotein cholesterol; LM = lean mass; MAP = mean arterial pressure; PP = pulse pressure; SBP = systolic blood pressure; SFA = subcutaneous fat area; TC = total cholesterol; TFA = total fat area; VFA = visceral fat area.

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• Figure 1. 

  Maximum oxygen uptake before and after 12-week aerobic exercise intervention in overweight and obese men. Data are expressed as mean ± SE.

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• Figure 2. 

  Arterial compliance and β-stiffness index before and after 12-week aerobic exercise intervention in overweight and obese men. Data are expressed as mean ± SE.

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• Figure 3. 

  Plasma ET-1 and NO_x (stable end product of nitric oxide) concentrations before and after 12-week aerobic exercise intervention in overweight and obese men. Data are expressed as mean ± SE.

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Discussion 

In the present study, we determined the central arterial distensibility and endothelial function in overweight and obese men before and after a 12-week aerobic exercise training-induced weight reduction program. After the exercise program, the BMI markedly decreased, the carotid arterial compliance significantly increased, and the β-stiffness index decreased. Thus, weight reduction by aerobic exercise induced an increase in central arterial distensibility among overweight and obese men. We also demonstrated that the aerobic exercise training-induced weight loss program significantly decreased the plasma ET-1 concentration and markedly increased the plasma NO_x—a stable end product of NO concentration—among overweight and obese men, suggesting an improvement in endothelial function. Therefore, we suggest that increased central arterial distensibility using a 12-week aerobic exercise training-induced weight loss program might also contribute to an improvement in endothelial function.

Reduced arterial distensibility has been implicated in the pathophysiology of cardiovascular disease and identified as an independent risk factor for cardiovascular disease.¹², ¹³, ¹⁴ Several studies have demonstrated that obese subjects have lower degrees of arterial distensibility.¹⁵, ¹⁶, ¹⁷ Danias et al¹⁵ have shown that obese men have lower aortic elasticity than do age-matched nonobese men. Furthermore, it has been reported that the aortic pulse wave velocity, a traditional index of arterial stiffness, is greater in middle-age overweight and obese adults than in age-matched normal-weight adults.¹⁷ Taken together, these findings clearly demonstrate that arterial distensibility in overweight and obese humans is lower than in normal-weight humans. In the present study, we have demonstrated for the first time that aerobic exercise training-induced weight loss increased arterial compliance and decreased the β-stiffness index in overweight and obese men. These findings suggest that weight reduction through habitual aerobic exercise induces an increase in central arterial distensibility in overweight and obese men, which might have beneficial effects vis-à-vis the prevention of cardiovascular disease.

Many studies have shown that regular aerobic exercise is associated with greater central distensibility⁵, ¹⁸, ¹⁹; however, it is not known whether aerobic exercise training influences arterial distensibility in overweight and obese adults. In the present study, we found that central arterial distensibility, as assessed by the carotid arterial compliance and the β-stiffness index, increased with aerobic exercise training in overweight and obese men. Thus, habitual aerobic exercise produces beneficial effects with respect to central arterial distensibility in overweight and obese adults. We suggest that regular aerobic exercise is an important strategy that can be applied to prevent the occurrence of vascular disease in overweight and obese humans.

Obesity is also strongly associated with endothelial dysfunction, which might play a role in the development of decreased arterial distensibility.⁵, ²⁰, ²¹, ²², ²³ Vascular endothelial cells produce some vasoactive substances (i.e., ET-1 and NO).²⁴, ²⁵ ET-1, which is produced by vascular endothelial cells, has potent vasoconstrictor and proliferative activity on vascular smooth muscle cells.²⁴, ²⁶ Previous studies have reported that arterial distensibility was decreased by the intra-arterial infusion of ET-1 and increased by the administration of an ET-1 receptor antagonist.²⁷, ²⁸ NO produced by vascular endothelial cells has a potent vasodilator effect and plays an important role in regulating platelet vessel wall interactions and vascular resistance and growth.²⁵ Wilkinson et al²⁹ reported that arterial distensibility decreased after intra-arterial infusion of a NO synthase inhibitor. These findings suggest that endogenous ET-1 and NO participate in the regulation of arterial distensibility. In the present study, we have demonstrated that the plasma ET-1 concentration was decreased and the plasma NO_x concentration increased by aerobic exercise training-induced weight reduction in overweight and obese men. Taken together, these data suggest that the increase in central arterial distensibility by exercise training-induced weight loss might contribute to an improvement in endothelial function, as assessed by ET-1 and NO, after an aerobic exercise training-induced weight-reduction program in overweight and obese men.

The present study, however, had several limitations. First, the present study might have had a measurement bias because of the lack of blinding. Second, other confounders might have been responsible for cardiovascular health. Third, it was not apparent whether the weight loss or the aerobic exercise had an effect on arterial function.

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