Vitamin D regulates apoptosis in adipocytes via Ca2+ signaling

Abstract

Modulation of apoptosis is emerging as a promising strategy for prevention and treatment of obesity because removal of adipocytes through this process will result in reducing body fat and long‐lasting maintenance of weight loss. Effects of vitamin D on apoptotic cell death are mediated via multiple signaling pathways that involve common regulators and effectors converging on cellular Ca2+ (Sergeev, 2009). The vitamin D‐regulated Ca2+‐dependent apoptotic molecular targets in adipose tissue have not been identified. We investigated mechanism of 1,25(OH)2‐vitamin D3 (1,25D)‐induced apoptosis using mouse 3T3‐L1 adipocytes. The results obtained demonstrated that 1,25D induces, in concentration‐ and time‐dependent fashion, the apoptotic Ca2+ signal ‐ a sustained, prolonged increase in concentration of intracellular Ca2+ ‐ in mature, accumulating lipids adipocytes. The 1,25D‐induced increase in cellular Ca2+ was associated with activation of the Ca2+‐dependent μ‐calpain and the Ca2+/calpain‐dependent caspase‐12. The activation of these proteases was sufficient for effecting morphological and biochemical changes attributed to apoptosis. These findings imply that the 1,25D‐induced cellular Ca2+ signal can act as an apoptotic initiator that directly recruits Ca2+‐dependent apoptotic effectors capable of executing apoptosis in adipose tissue. Targeting of the adipocyte Ca2+ signaling with vitamin D may represent an effective, safe and affordable approach to the prevention and treatment of obesity.Supported by USDA 2009‐35200‐05008 and USDA SD00H325.