| Objective To explore the role of androgen and androgen receptor (AR) in exercise-induced bone strength including the increase of bone mineral density (BMD), bone mass, and bone biomechanical properties in high-fat diet mice. Methods Castration and AR-blockaded mouse models were established using castration surgery (Cas) and neck-embedded AR antagonist flutamide (F) releasing pellets, respectively. For exploring the effects of androgen and AR on exercise-induced bone strength, HFD mice were divided into 6 groups after 8-week high-fat diet, HFD, HFD+E, HFD+Cas, HFD+Cas+E, HFD+F, and HFD+F+E groups, with 6 mice in each group. Mice in exercise groups participated in 6-week moderate-intensity aerobic exercise, 1 h/day, 6 days/week. Samples were collected within 36 h after the last exercise. Femur and tibia wet weights were weighed using electronic balance. Serum testosterone level was detected with ELISA. BMD and bone mass of the left femur were assessed with micro-CT. Biomechanical properties of the right femur were determined with three-point bending test. The protein levels of AR, IGF-1, and IGF-1R were detected using Western blotting. Results (1) HFD significantly decreased the levels of serum testosterone, femur and tibia wet weight, BMD, and bone mass in mice. Six-week aerobic exercise significantly improved the above indicators (except for SMI) and bone biomechanical properties in HFD mice. (2) Castration reversed the improving effects of aerobic exercise on serum testosterone, BMD, bone mass, and bone biomechanical properties in HFD mice. The benefits of aerobic exercise on trabecular BMD, bone mass and bone microstructure, and bone biomechanical properties in HFD mice were reversed by AR antagonist. (3) The exercise-induced increases of AR, IGF-1, and IGF-1R proteins in the bone of HFD mice were completely blocked by castration or AR blocking. Conclusion Androgen/AR plays important roles in aerobic exercise-induced increases of BMD in cancellous bone, bone mass, and bone biomechanical properties in high-fat diet mice, which may be fulfilled by androgen/AR mediated increases of IGF-1/IGF-1R in the bone. |