INTRODUCTION: An important mechanism by which physical activity reduces the risk of cardiovascular disease is through regulating plasma lipids. We investigated whether low-intensity exercise modulates lipid metabolism and the transcription factors peroxisome proliferator-activated receptor gamma (PPARgamma) and liver X receptor alpha (LXRalpha) responsible for controlling reverse cholesterol transport (RCT). METHODS: Thirty-four sedentary adults, mean age 45.6 +/- 11.1 yr, participated in an 8-wk low-intensity exercise program consisting of walking 10,000 steps, three times a week. Subjects were randomly allocated to either an exercise group or a sedentary control group, and serum lipid or lipoprotein concentrations were determined. RESULTS: Compared with controls, there was a significant decrease in total cholesterol (preexercise 5.73 +/- 1.39 mmol/L; postexercise 5.32 +/- 1.28 mmol/L) and a significant increase in HDL (preexercise 1.46 +/- 0.47 mmol/L; postexercise 1.56 +/- 0.50 mmol/L) after the exercise program. There was a significant increase in serum oxidized LDL (oxLDL) concentrations in the exercise group before and after exercise (0 wk 554 +/- 107 ng/mL; 4 wk 698 +/- 134 ng/mL; 8 wk 588 +/- 145 ng/mL). A significant increase in leukocyte mRNA expression for PPARgamma (4 wk 1.8 +/- 0.9-fold; 8 wk 4.3 +/- 1.9-fold) was observed, which was reinforced by increased PPARgamma DNA-binding activity postexercise (preexercise 0.22 +/- 0.09 OD units; postexercise 1.13 +/- 0.29 OD units). A significant increase in gene expression was observed for the oxLDL scavenger receptor CD36 (4 wk 3.8 +/- 0.6-fold; 8 wk 2.7 +/- 0.5-fold) and LXRalpha (8 wk 3.5 +/- 0.8-fold). Two LXRalpha-regulated genes involved in RCT, namely, ATP-binding cassette transporters A1 and GI (ABCA1 and ABCG1, respectively), were significantly up-regulated postexercise (8 wk: ABCA1 3.46 +/- 0.56-fold; ABCG1 3.06 +/- 0.47-fold). CONCLUSION: We propose that the net effect of these changes may be to increase oxLDL uptake, to stimulate RCT, and thus to promote clearance of proatherogenic lipids from the vasculature, ultimately contributing to the cardiovascular benefits of low-intensity aerobic exercise.

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