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Role of uncoupling protein 2 (UCP2) expression and 1α, 25‐dihydroxyvitamin D 3 in modulating adipocyte apoptosis
Author(s) -
Sun Xiaocun,
Zemel Michael B.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-1971fje
Subject(s) - apoptosis , endocrinology , medicine , adipocyte , calcium , mitochondrion , adipose tissue , chemistry , biology , microbiology and biotechnology , biochemistry
We previously found that 1α, 25‐dihydroxyvitamin D 3 [1α, 25‐(OH) 2 ‐D 3 ] modulates adipocyte lipid metabolism via a Ca 2+ ‐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 ‐D 3 levels. However, because UCP2 reduces mitochondrial potential, we have evaluated the roles of UCP2, mitochondrial uncoupling, and 1α, 25‐(OH) 2 ‐D 3 in adipocyte apoptosis. Overexpressing UCP2 in 3T3‐L1 cells induced marked reductions in mitochondrial potential (∆ψ) and ATP production ( P <0.01), increases in the expression of caspases ( P <0.05), and a decrease in Bcl‐2/Bax expression ratio ( P <0.01). Physiological doses of 1α, 25‐(OH) 2 ‐D 3 (0.1–10 nM) restored mitochondrial ∆ψ in LI‐UCP2 cells and protected against UCP2 overexpression‐induced apoptosis ( P <0.01), whereas a high dose (100 nM) stimulated apoptosis in 3T3‐L1 and L1‐UCP2 cells ( P <0.05). 1α, 25‐(OH) 2 ‐D 3 stimulated cytosolic Ca 2+ dose‐dependently in both 3T3‐L1 and L1‐UCP2 cells. However, physiological doses suppressed mitochondrial Ca 2+ levels by ~50% whereas the high dose increased mitochondrial Ca 2+ by 25% ( P <0.05); this explains stimulation of apoptosis by the high dose of 1α, 25‐(OH) 2 ‐D 3 . Using high‐calcium diets to suppress 1α, 25‐(OH) 2 ‐D 3 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.