Premium
1α,25‐dihydroxyvitamin D 3 inhibits uncoupling protein 2 expression in human adipocytes
Author(s) -
Shi Hang,
Norman Anthony W.,
Okamura William H.,
Sen Anindita,
Zemel Michael B.
Publication year - 2002
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.02-0255fje
Subject(s) - medicine , endocrinology , adipocyte , chemistry , uncoupling protein , receptor , lipogenesis , calcitriol receptor , thermogenesis , lipolysis , fatty acid , adipose tissue , biology , vitamin d and neurology , brown adipose tissue , biochemistry
We recently demonstrated that suppressing 1α,25‐(OH) 2 ‐D 3 by increasing dietary calcium decreases adipocyte intracellular Ca 2+ ([Ca 2+ ] i ), stimulates lipolysis, and inhibits lipogenesis. High calcium diets also increase core temperature and white adipose tissue uncoupling protein 2 (UCP2) expression in aP2‐agouti transgenic mice. Accordingly, we have evaluated the role of 1α,25‐(OH) 2 ‐D 3 in regulating human adipocyte UCP2 expression. Treatment of human adipocytes for 48 h with 1 nM 1α,25‐(OH) 2 ‐D 3 inhibited UCP2 mRNA and protein levels by 50% (P<0.002) and completely blocked isoproterenol‐ or fatty acid‐stimulated two‐ to threefold increases in UCP2 expression. However, a specific agonist for the membrane vitamin D receptor (mVDR), 1α,25‐dihydroxylumisterol3, was unable to inhibit basal, isoproterenol‐stimulated, or fatty acid‐stimulated UCP2 expression, whereas a specific mVDR antagonist,1β,25dihydroxyvitamin D 3 , was unable to prevent the 1α,25‐(OH) 2 ‐D 3 inhibition of UCP2 expression. In contrast, nuclear vitamin D receptor (nVDR) knockout via antisense oligodeoxynucleotide (ODN) prevented the inhibitory effect of 1α,25‐(OH) 2 ‐D 3 on adipocyte UCP2 expression and protein levels. These data indicate that 1α,25‐(OH) 2 ‐D 3 exerts an inhibitory effect on adipocyte UCP2 expression via the nVDR. Thus, suppression of 1α,25‐(OH) 2 ‐D 3 and consequent up‐regulation of UCP2 may contribute to our previous observation of increased thermogenesis in mice fed with high calcium diets.