Weight Loss via Exercise with Controlled Dietary Intake May Affect Phospholipid Profile for Cancer Prevention in Murine Skin Tissues

Abstract

Exercise has been linked to a reduced cancer risk in animal models. However, the underlying mechanisms are unclear. This study assessed the impact of exercise with dietary consideration on the phospholipid profile in TPA-induced mouse skin tissues. CD-1 mice were randomly assigned to one of the three groups: ad libitum-fed sedentary control, ad libitum-fed treadmill exercise at 13.4 m/min for 60 min/d, 5 d/wk (Ex+AL), and treadmill exercised but pair-fed with the same amount as the control (Ex+PF). After 14 wks, Ex+PF but not Ex+AL mice demonstrated ~25% decrease in both body weight and body fat when compared to the controls. Of the total 338 phospholipids determined by electrospray ionization tandem mass spectrometry, 57 were significantly changed, and 25 species could distinguish effects of exercise and diet treatments in a stepwise discriminant analysis. A 36-75% decrease of phosphatidylinositol (PI) levels in Ex+PF mice occurred along with a significant reduction of PI3K in TPA-induced skin epidermis, as measured by both western blotting and immunohistochemistry. In addition, near 2-fold increase of the long chain polyunsaturated fatty acids, docosahexaenoic and docosapentaenoic acids, in phosphatidylcholines, phosphatidylethanolamines, and lysophosphatidylethanolamines wasobserved in the Ex+PF group. Microarray analysis indicated that the expression of fatty acid elongase-1 increased. Taken together, these data indicate that exercise with controlled dietary intake but not exercise alone significantly reduced body weight and body fat as well as modified the phospholipid profile, which may contribute to cancer prevention by reducing TPA-induced PI3K and by enhancing -3 fatty acid elongation.