High vitamin D and calcium intakes reduce diet‐induced obesity in mice by increasing adipose tissue apoptosis

Scope Modulation of apoptosis is emerging as a promising antiobesity strategy because removal of adipocytes through this process will result in reducing body fat. Effects of vitamin D on apoptosis are mediated via multiple signaling pathways that involve common regulators and effectors converging on cellular C a 2+ . We have previously shown that 1,25‐dihydroxyvitamin D 3 induces the C a 2+ signal associated with activation of C a 2+ ‐dependent apoptotic proteases in mature adipocytes. In this study, a diet‐induced obesity ( DIO ) mouse model was used to evaluate the role of vitamin D and calcium in adiposity. Methods and results DIO mice fed high vitamin D 3 , high C a, and high D 3 plus high C a diets demonstrated a decreased body and fat weight gain, improved markers of adiposity and vitamin D status (plasma concentrations of glucose, insulin, adiponectin, 25‐hydroxyvitamin D , 1,25‐dihydroxyvitamin D , parathyroid hormone ( PTH )), but an increased plasma C a 2+ . High D 3 and C a intakes were associated with induction of apoptosis and activation of C a 2+ ‐dependent apoptotic proteases, calpain and caspase‐12, in adipose tissue of DIO mice. The combination of D 3 plus C a was more effective than D 3 or C a alone in decreasing adiposity. Conclusion The results imply that high vitamin D and C a intakes activate the C a 2+ ‐mediated apoptotic pathway in adipose tissue. Targeting this pathway with vitamin D and C a supplementation could contribute to the prevention and treatment of obesity. However, this potentially effective and affordable approach needs to be evaluated from a safety point of view.