Inhibition of androgen receptor can decrease fat metabolism by decreasing carnitine palmitoyltransferase I levels in skeletal muscles of trained mice

Abstract

Background Androgen hormone levels are strongly associated with obesity in adult mammals, especially with advanced age. We investigated androgen receptor inhibition on fat metabolism and long-chain fatty acid (LCFA) transport proteins in skeletal muscle during exercise. Methods Male ICR mice were randomly divided into three groups: CON (control), EX (exercise), and EXIN (exercise + androgen receptor inhibition). EX and EXIN groups were trained on a treadmill five times a week. After 4 weeks, the fat metabolism of each group was measured using open-circuit calorimetry during 1 hour of exercise. After the metabolism measurement, the expression levels of LCFA transport proteins (FAT/CD36, CPTI) were analyzed in skeletal muscle. Results Weight gain and final body weight were significantly lower in the EX group than in either the CON or EXIN groups. Conversely, food intake was significantly higher in the EX group than it was in the CON and EXIN groups. The total weight (CON; 2.07 +/- 0.6, EX; 1.64 +/- 0.2, EXIN; 1.95 +/- 0.2) of the abdominal adipose tissue were significantly lower in the EX group than in the CON and EXIN groups (P < 0.05). However, there was no different between the CON and EXIN group. Oxygen uptake and fat oxidation during exercise tended to be lower (12%) in the EXIN group than in the EX group. Total fat oxidation in the EXIN group was significantly lower during the initial 20-min (P < 0.003) and 40-min (P < 0.041) phases compared to that in the EX group. In addition, the level of FAT/CD36 protein in the EX and EXIN groups was approximately double that in the CON group (P < 0.001, P < 0.001). CPTI expression in the EX group was higher than that in the EX group (P < 0.0069) as well as in the CON group. Conclusion Exercise training increases the expression of LCFA transport proteins (FAT/CD36, CPTI). Blocking androgen receptors can decreases the expression of CPTI in the skeletal muscle, which reduces fat metabolism. Thus, reducing sex hormones or suppressing the sensitivity of AR receptors can inhibit energy efficiency and fat metabolism by suppressing CPTI.