Elsevier

Atherosclerosis

Volume 212, Issue 1, September 2010, Pages 230-236
Atherosclerosis

Exercise training accelerates the removal from plasma of LDL-like nanoemulsion in moderately hypercholesterolemic subjects

https://doi.org/10.1016/j.atherosclerosis.2010.04.030Get rights and content

Abstract

Objective

Exercise training improves plasma lipid profile and diminishes risk of coronary heart disease. Previously, we showed that training increases LDL plasma clearance, as tested by an artificial LDL-like nanoemulsion method, presumably by increasing LDL receptor activity. In this study, we investigated whether training could also improve LDL clearance in hypercholesterolemic subjects (HCh) that are exposed to increased risk of cardiovascular events.

Methods

Twenty sedentary HCh and 20 normolipidemic (NL) sedentary volunteers were divided into four groups: 12 HCh submitted to 4-month training program, 8 HCh with no exercise program, 12 NL submitted to 4-month training and 8 NL with no exercise program. An LDL-like nanoemulsion labeled with 14C-cholesteryl ester was injected intravenously into all subjects and plasma samples were collected during 24 h after injection to determine the fractional clearance rate (FCR, in h−1) by compartmental analysis. The study was performed on the first and on the last day of the 4-month study period.

Results

In both, trained HCh and NL groups, training increased nanoemulsion FCR by 36% (0.0443 ± 0.0126; 0.0602 ± 0.0187, p = 0.0187 and 0.0503 ± 0.0203; 0.0686 ± 0.0216, p = 0.0827, respectively). After training, LDL cholesterol diminished in both HCh and NL groups. In HCh, but not in NL group, LDL susceptibility to oxidation decreased, but oxidized LDL was unchanged. In both non-trained groups FCR was the same for the last and the 4-month previous evaluation.

Conclusion

In HCh, exercise training increased the removal of LDL as tested by the nanoemulsion, and this probably accounted for decreased LDL cholesterol and diminished LDL susceptibility to oxidation.

Introduction

Exercise training usually decreases the concentration of fasting plasma triacylglycerols that reflect the status of very low density lipoprotein (VLDL) and also tends to increase high density lipoprotein (HDL) cholesterol [1], [2]. Those effects are consistently beneficial regarding prevention of coronary heart disease (CHD) and may, at least in part, account for the diminished risk of developing CHD in trained individuals [3]. However there is controversy on whether exercise training diminishes LDL cholesterol, a major CHD risk factor. There are perhaps different effects pending on whether the individuals have normal or elevated levels of LDL cholesterol [4], [5], [6].

In a previous study, we showed that, in athletes and sedentary subjects with equal LDL cholesterol, the plasma clearance of LDL, probed by the LDL-like nanoemulsion approach, was greater in athletes than in sedentary subjects. The increased LDL turnover in athletes would protect the lipoprotein from lipid oxidability and peroxidation since the lipoprotein would be less exposed to those deleterious changes. In fact, the levels of oxidized LDL in exercise-trained subjects were lower than those of sedentaries [5]. This was found despite increased generation of reactive oxygen species during exercise training sessions [7], [8].

LDL cholesterol concentration in the plasma is regulated by the balance between synthesis by the liver and removal from the plasma by lipoprotein receptors. Hypercholesterolemia is basically caused by defects in removal of LDL from the plasma rather than increases in lipoprotein synthesis [9]. Moderate hypercholesterolemia affects a substantial proportion of the population, exposing subjects to elevated risk of developing CHD.

In this study, the hypothesis was raised whether exercise training could also increase the removal of the lipoprotein from the plasma of sedentary moderately hypercholesterolemic subjects and decrease the LDL oxidability.

As in our previous studies, LDL intravascular metabolism was probed by LDL-like nanoemulsions. The validity of the artificial nanoemulsion method to explore the LDL metabolism was demonstrated in several studies [5], [10], [11], [12], [13]. The nanoemulsion particles are manufactured without protein, but after injection into the bloodstream they acquire several exchangeable apolipoproteins such as apo E that is recognized by the LDL receptor. Thus, the nanoemulsion is internalized into the cells by LDL receptor-mediated endocytosis [9], [10]. The results of the study show that exercise training contributes to improve the regulation of the intravascular lipid metabolism in hypercholesterolemic subjects.

Section snippets

Study subjects

Twenty hypercholesterolemic (HCh) sedentary volunteers, with LDL-C between 130 and 190 mg/dL and 20 normolipidemic (NL) sedentary volunteers, with LDL-C below 130 mg/dL were included in the study. After preliminary screening and baseline assessments, they were assigned to four study groups:

  • -

    HCh with training: 12 subjects (8 males and 4 females) aged 20–60 (40 ± 13, mean ± SD) years were studied twice, at baseline and after a 4-month exercise training program.

  • -

    HCh without training: 8 subjects (4 males

Results

There were no differences between HCh with and HCh without training regarding the values of age, body mass index, abdominal circumference, VO2 peak, plasma lipids, apolipoproteins, oxidized LDL, susceptibility of LDL to oxidation and FCR of the nanoemulsion label. Similarly, those values did not differ between NL with and without exercise training (Table 1).

In Table 1 it is shown that the 4-month exercise training program was effective in increasing VO2 peak in both groups of HCh and NL. The

Discussion

In this study, exercise training had favorable effects on the regulation of LDL intravascular metabolism in HCh subjects. Those effects increased the removal from plasma of the LDL-like nanoemulsion, indicating increased LDL clearance (p = 0.0187), a decrease in the LDL-cholesterol concentration (p = 0.0058) and a decreased LDL oxidability (p = 0.0039). Similarly, in NL exercise tended to increase the removal of the nanoemulsion and diminish the LDL cholesterol, although this trend was not

Conflict of interest

None declared.

Acknowledgments

This study was supported by Fundação do Amparo à Pesquisa do Estado de São Paulo (FAPESP), São Paulo, Brazil. Dr. Maranhão has a Research Grant from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brasilia, Brazil.

The authors are grateful to Mr. William A. Presada for revising the text, to Dr. Carlos H. Mesquita for guidance in the kinetic study data analysis.

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