Aerobic exercise training-induced bone and vascular adaptations in mice lacking adiponectin

Adiponectin regulates lipid and glucose metabolism, and insulin sensitivity in various target organs; however, the effects of adiponectin on bone health remain controversial. Exercise training can enhance bone density, bone microarchitecture, and blood flow. This study aimed to elucidate the role of adiponectin in adaptations of bone microarchitecture and bone vasculature in response to aerobic exercise training. Adult male C57BL/6 wild-type (WT) and homozygous adiponectin knockout (AdipoKO) mice were either treadmill exercise trained or remained sedentary for 8-10 weeks. The trabecular structures of the distal femoral metaphysis, a weight-bearing bone, and the mandible, a non-weight-bearing bone, were examined using microcomputed tomography. The femoral principal nutrient arteries were isolated to assess vasoreactivity (vasodilation and vasoconstriction) and structural remodeling. At the femoral metaphysis, impaired trabecular bone structures, including reduced connectivity density and increased trabecular spacing, were observed in AdipoKO mice compared to WT mice. In addition, nitric oxide-mediated, endothelium-dependent vasodilation was substantially reduced, and wall-to-lumen ratio was significantly increased in the femoral principal nutrient artery of AdipoKO mice. Interestingly, although exercise training-induced enhancements in trabecular connectivity density were observed at the femoral metaphysis of both WT and AdipoKO, increased vasoconstrictor responses were only observed in the femoral principal nutrient artery of WT mice, not in the AdipoKO mice. In mandibular trabecular bone, exercise training increased trabecular bone volume fraction (BV/TV, %) and intersection surface in the mandible of both WT and AdipoKO mice. These findings indicate that adiponectin is crucial for maintaining normal bone microarchitecture and vasculature. Although the absence of adiponectin compromises bone vascular adaptation to exercise training in mice, some exercise training-induced alterations in bone microarchitecture occurred in the absence of adiponectin, suggesting contribution of compensatory mechanisms during exercise training.