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

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.

Aerobical Physical Activities Improve Quality of Cardiac Health in an Animal Model: Parameters of Calorimetry, Profile Lipids and Oxidative Stress

“…These results are consistent with Kraus and Slentz [56] and Rocco et al [59] to report that exercise increased the HDL -cholesterol fraction and prevented the development of atherosclerosis.…”

Effects of aerobic exercise on lipids and lipoproteins

“…Kamani et al [72] found a significant decrease in mean PCSK9 levels and mean LDL-C levels in volunteers after 3 months exercise, and concluded that daily exercise is independently associated with a decrease in PCSK9 levels over time. Rideout et al [73] used C57BL/6 mice as a model, and feed them with high-fat diet, then make them do aerobic exercise. After 8 weeks, the levels of PCSK9 mRNA and sterol regulatory element binding protein 2 (SREBP2) were increased significantly in mice with high-fat diet and exercise training, 1.9 and 1.8 times higher than those only with high-fat diet respectively.…”

Regulation of reverse cholesterol transport - a comprehensive appraisal of available animal studies

“…However, a study by our group did not find any impact of voluntary wheel running on in vivo macrophage RCT in wild-type mice, even though cholesterol efflux from macrophage foam cells towards plasma of exercising mice in vitro was significantly increased [93]. On the other hand, macrophage RCT was higher in exercising human CETP transgenic mice when compared with sedentary controls [94]. This beneficial effect of regular exercise training on RCT was at least in part ascribed to a raise in plasma HDL cholesterol and an enhanced hepatic uptake of cholesterol through elevated LDL receptor protein expression [94].…”