Pronounced effect of voluntary running wheel exercise in combination with oral administration of caffeine to decrease tissue fat and increase UVB-induced apoptosis in the epidermis of SKH-1 mice

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Our previous studies showed an inhibitory effect of oral administration of caffeine or voluntary running wheel exercise on UVB-induced skin carcinogenesis in SKH-1 mice. Mechanistic studies indicated that exercise or caffeine administration decreased tissue fat and stimulated UVB-induced apoptosis in the epidermis as well as apoptosis in tumors in tumor-bearing mice. These effects were selective since administration of caffeine or voluntary exercise did not influence apoptosis in normal non-UVB-treated epidermis or in areas of the epidermis away from tumors in tumor-bearing mice.

In the present study, we found that treatment of SKH-1 mice orally with caffeine (0.1 mg/ml in the drinking water), voluntary running wheel exercise or a combination of caffeine and exercise for 2 weeks (a) decreased the weight of the parametrial fat pads by 40, 57 and 80%, respectively, (b) decreased the thickness of the dermal fat layer by 54, 48, and 75%, respectively, (c) stimulated UVB-induced apoptosis (sunburn cells) in the epidermis by 33, 113 and 333%, respectively, and (d) increased the percentage of immunoreactive caspase 3 (active form) positive cells in the epidermis by 42, 112 and 354%, respectively. Oral administration of caffeine (0.4 mg/ml in the drinking water) in combination with voluntary exercise did not cause a further increase in UVB-induced apoptosis. Similar results were observed in a second experiment. Although voluntary exercise or orally administrated caffeine (0.1 mg/ml in the drinking water) for 2 weeks only caused a small stimulation of UVB-induced increase in the level of phospho-p53 (Ser15) (15%), the combination of the two treatments caused a substantial stimulation of UVB-induced increase in phospho-p53 (Ser15) (100%). The addition of low dose caffeine treatment to the running wheel exercise regimen stimulated running wheel activity by ~14%. The results of these studies suggest a synergistic effect of combined voluntary exercise and oral administration of a low dose of caffeine on UVB-induced apoptosis. (Supported by NIH Grant RO3 CA 121418).