Voluntary exercise together with oral caffeine markedly stimulates UVB light-induced apoptosis and decreases tissue fat in SKH-1 mice

Abstract

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 (i) decreased the weight of the parametrial fat pads by 35, 62, and 77%, respectively; (ii) decreased the thickness of the dermal fat layer by 38, 42, and 68%, respectively; (iii) stimulated the formation of UVB-induced apoptotic sunburn cells in the epidermis by 96, 120, and 376%, respectively; and (iv) stimulated the formation of UVB-induced caspase 3 (active form)-positive cells in the epidermis by 92, 120, and 389%, respectively (average of two experiments). Oral administration of caffeine (0.4 mg/ml in the drinking water) in combination with voluntary exercise was less effective than administration of the low dose of caffeine in combination with exercise in stimulating UVB-induced apoptosis. Although orally administrated caffeine (0.1 mg/ml in the drinking water) or voluntary exercise for 2 weeks caused only a small nonsignificant stimulation of UVB-induced increase in the percentage of phospho-p53 (Ser-15)-positive cells in the epidermis (27 or 18%, respectively), the combination of the two treatments enhanced the UVB-induced increase in phospho-p53 (Ser-15)-positive cells by 99%. The plasma concentration of caffeine in mice ingesting caffeine (0.1-0.4 mg/ml drinking water) is similar to that in the plasma of most coffee drinkers (one to four cups per day). Our studies indicate a greater than additive stimulatory effect of combined voluntary exercise and oral administration of a low dose of caffeine on UVB-induced apoptosis.

Fig. 1.

Effect of voluntary RW exercise, oral administration of caffeine, or a combination of exercise and caffeine on tissue fat. SKH-1 mice (10 per group) were treated with RW exercise, oral caffeine [0.1 or 0.4% in the drinking water (0.1 or 0.4 CF)], or a combination of RW and CF for 2 weeks. The weight of the parametrial fat pads and the thickness of the dermal fat layer were determined. Using Tukey's multiple comparison test for parametrial fat pad measurements, we found that the CF (0.1) + RW group was different from the CF (0.1) group in experiments 1 and 2. For the thickness of the dermal fat layer, the CF (0.1) + RW group was different from the CF (0.1) group in experiment 1 and from the RW group in experiments 1 and 2. When we combined data from experiments 1 and 2, the dermal fat thickness from animals treated with CF (0.1) + RW was significantly different from the dermal fat thickness in animals treated with CF (0.1) (P < 0.01).

Fig. 2.

Effect of voluntary RW exercise, oral administration of caffeine, or a combination of exercise and caffeine on UVB-induced apoptosis in the epidermis. SKH-1 mice (10 per group) were treated with RW exercise, oral caffeine [0.1 or 0.4% in the drinking water (0.1 or 0.4 CF)], or a combination of RW and CF for 2 weeks. Apoptotic sunburn cells and caspase 3 (active form)-positive cells in the epidermis were determined at 6 h after irradiation with UVB (30 mJ/cm²). Using Tukey's multiple comparison test for apoptotic sunburn cell measurements, we found that the CF (0.1) + RW group was different from the CF (0.1) group in experiments 1 and 2 and from the RW group in experiments 1 and 2. For the caspase 3 measurements, the CF (0.1) + RW group was different from the CF (0.1) group in experiments 1 and 2 and from the RW group in experiments 1 and 2.

Fig. 3.

Effect of voluntary RW exercise, oral administration of caffeine, or a combination of exercise and caffeine on UVB-induced increase in phospho-p53 (Ser-15). SKH-1 mice (10 per group) were treated with RW exercise, oral caffeine [0.1 or 0.4% in the drinking water (0.1 or 0.4 CF)], or a combination of RW and CF for 2 weeks. Phospho-p53 (Ser-15)-positive cells in the epidermis were determined. Using Tukey's multiple comparison test for phospho-p53 (Ser-15)-positive cell measurements, we found that the CF (0.1) + RW group was different from the CF (0.1) group in experiments 1 and 2 and from the RW group in experiments 1 and 2.