• Apoptosis;
  • Calcium;
  • Calpain;
  • Caspase-12;
  • Diet-induced obesity;
  • Vitamin D


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 Ca2+. We have previously shown that 1,25-dihydroxyvitamin D3 induces the Ca2+ signal associated with activation of Ca2+-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 D3, high Ca, and high D3 plus high Ca 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 Ca2+. High D3 and Ca intakes were associated with induction of apoptosis and activation of Ca2+-dependent apoptotic proteases, calpain and caspase-12, in adipose tissue of DIO mice. The combination of D3 plus Ca was more effective than D3 or Ca alone in decreasing adiposity.


The results imply that high vitamin D and Ca intakes activate the Ca2+-mediated apoptotic pathway in adipose tissue. Targeting this pathway with vitamin D and Ca 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.