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Aerobic Exercise Improves Reverse Cholesterol Transport in Cholesteryl Ester Transfer Protein Transgenic Mice

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Lipids

Abstract

We analyzed the effect of a 6-week aerobic exercise training program on the in vivo macrophage reverse cholesterol transport (RCT) in human cholesteryl ester transfer protein (CETP) transgenic (CETP-tg) mice. Male CETP-tg mice were randomly assigned to a sedentary group or a carefully supervised exercise training group (treadmill 15 m/min, 30 min sessions, five sessions per week). The levels of plasma lipids were determined by enzymatic methods, and the lipoprotein profile was determined by fast protein liquid chromatography (FPLC). CETP activity was determined by measuring the transfer rate of 14C-cholesterol from HDL to apo-B containing lipoproteins, using plasma from CETP-tg mice as a source of CETP. The reverse cholesterol transport was determined in vivo by measuring the [3H]-cholesterol recovery in plasma and feces (24 and 48 h) and in the liver (48 h) following a peritoneal injection of [3H]-cholesterol labeled J774-macrophages into both sedentary and exercise trained mice. The protein levels of liver receptors were determined by immunoblot, and the mRNA levels for liver enzymes were measured using RT-PCR. Exercise training did not significantly affect the levels of plasma lipids or CETP activity. The HDL fraction assessed by FPLC was higher in exercise-trained compared to sedentary mice. In comparison to the sedentary group, a greater recovery of [3H]-cholesterol from the injected macrophages was found in the plasma, liver and feces of exercise-trained animals. The latter occurred even with a reduction in the liver CYP7A1 mRNA level in exercised trained animals. Exercise training increased the liver LDL receptor and ABCA-1 protein levels, although the SR-BI protein content was unchanged. The RCT benefit in CETP-tg mice elicited by exercise training helps to elucidate the role of exercise in the prevention of atherosclerosis in humans.

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Abbreviations

ABC:

Transporters ABCA-1 and ABCG-1

AcLDL:

Acetylated LDL

Apo AI:

Apolipoprotein AI

Apo E:

Apolipoprotein E

B-E:

Low density lipoprotein receptor

CETP:

Cholesteryl ester transfer protein

CYP7A1:

7 alpha hydroxylase

CYP27A:

27 alpha hydroxylase

EC:

Esterified cholesterol

EDTA-PBS:

Ethylene diamine tetra acetic phosphate-buffered saline

FPLC:

Fast protein liquid chromatography

HDL:

High density lipoprotein

LCAT:

Lecithin cholesterol acyltransferase

LDL:

Low density lipoprotein

LRP:

LDL-receptor related protein

LXR:

Liver X receptor

LP:

Lipoprotein

RCT:

Reverse cholesterol transport

SR-BI:

Scavenger receptor class B type I

VLDL:

Very low density lipoprotein

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Acknowledgments

This work was supported by Fundação de Amparo à Pesquisa do Estado de Sao Paulo—FAPESP [07/50387-8 to MP, 06/52702-5 to DDFM Rocco, 07/56654-8 to LS Okuda and 09/53412-9 to RS Pinto] and by Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq [870248/1197-9 to DDFMR]. The authors are indebted to Dr. Marisa Dolhnikoff and Ana L B Silveira from the Pathology Museum, Faculty of Medical Sciences, University of Sao Paulo for helping with microscope analysis, and to Walter Campestre (LIM-16) and Antonio dos Santos Filho (LIM-17) for caring for the animals. The authors are thankful to Fundação Faculdade de Medicina and Laboratórios de Investigação Médica (LIM). Results of the present study do not constitute endorsement by ACSM.

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Authors and Affiliations

  1. Lipids Laboratory (LIM-10), Faculty of Medical Sciences, University of Sao Paulo, Av. Dr. Arnaldo 455, room 3305, Sao Paulo, SP, CEP 01246000, Brazil

    D. D. F. M. Rocco, L. S. Okuda, R. S. Pinto, F. D. Ferreira, E. R. Nakandakare, E. C. R. Quintão, S. Catanozi & M. Passarelli

  2. Emergency Care Research Unit (LIM-51), Faculty of Medical Sciences, University of Sao Paulo, Sao Paulo, Brazil

    S. K. Kubo

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  1. D. D. F. M. Rocco
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  2. L. S. Okuda
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  3. R. S. Pinto
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  7. E. C. R. Quintão
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  8. S. Catanozi
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  9. M. Passarelli
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Correspondence to M. Passarelli.

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Rocco, D.D.F.M., Okuda, L.S., Pinto, R.S. et al. Aerobic Exercise Improves Reverse Cholesterol Transport in Cholesteryl Ester Transfer Protein Transgenic Mice. Lipids 46, 617–625 (2011). https://doi.org/10.1007/s11745-011-3555-z

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  • DOI: https://doi.org/10.1007/s11745-011-3555-z

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