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