Role of uncoupling protein 2 (UCP2) expression and 1α, 25‐dihydroxyvitamin D 3 in modulating adipocyte apoptosis

Abstract

We previously found that 1α, 25-dihydroxyvitamin D₃ [1α, 25-(OH)₂-D₃] modulates adipocyte lipid metabolism via a Ca²⁺-dependent mechanism and inhibits adipocyte UCP2 expression, indicating that the anti-obesity effects of dietary calcium are mediated by suppression of 1α, 25-(OH)₂-D₃ levels. However, because UCP2 reduces mitochondrial potential, we have evaluated the roles of UCP2, mitochondrial uncoupling, and 1α, 25-(OH)₂-D₃ in adipocyte apoptosis. Overexpressing UCP2 in 3T3-L1 cells induced marked reductions in mitochondrial potential (∆ψ) and ATP production (PPP2-D₃ (0.1–10 nM) restored mitochondrial ∆ψ in LI-UCP2 cells and protected against UCP2 overexpression-induced apoptosis (PP2-D₃ stimulated cytosolic Ca²⁺ dose-dependently in both 3T3-L1 and L1-UCP2 cells. However, physiological doses suppressed mitochondrial Ca²⁺ levels by ~50% whereas the high dose increased mitochondrial Ca²⁺ by 25% (P2-D₃. Using high-calcium diets to suppress 1α, 25-(OH)₂-D₃ stimulated adipose tissue apoptosis in aP2 transgenic mice (P<0.01), suggesting that increasing dietary calcium stimulates adipose apoptosis and thereby further contributes to an anti-obesity effect of dietary calcium.