PMID- 12223452
OWN - NLM
STAT- MEDLINE
DCOM- 20021216
LR  - 20220311
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 16
IP  - 13
DP  - 2002 Nov
TI  - 1alpha,25-dihydroxyvitamin D3 inhibits uncoupling protein 2 expression in human 
      adipocytes.
PG  - 1808-10
AB  - We recently demonstrated that suppressing 1alpha,25-(OH)2-D3 by increasing 
      dietary calcium decreases adipocyte intracellular Ca2+ ([Ca2+]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 
      1alpha,25-(OH)2-D3 in regulating human adipocyte UCP2 expression. Treatment of 
      human adipocytes for 48 h with 1 nM 1alpha,25-(OH)2-D3 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), 
      1alpha,25-dihydroxylumisterol3, was unable to inhibit basal, 
      isoproterenol-stimulated, or fatty acid-stimulated UCP2 expression, whereas a 
      specific mVDR antagonist,1beta,25-dihydroxyvitamin D3, was unable to prevent the 
      1alpha,25-(OH)2-D3 inhibition of UCP2 expression. In contrast, nuclear vitamin D 
      receptor (nVDR) knockout via antisense oligodeoxynucleotide (ODN) prevented the 
      inhibitory effect of 1alpha,25-(OH)2-D3 on adipocyte UCP2 expression and protein 
      levels. These data indicate that 1a,25-(OH)2-D3 exerts an inhibitory effect on 
      adipocyte UCP2 expression via the nVDR. Thus, suppression of 1alpha,25-(OH)2-D3 
      and consequent up-regulation of UCP2 may contribute to our previous observation 
      of increased thermogenesis in mice fed with high calcium diets.
FAU - Shi, Hang
AU  - Shi H
AD  - University of Tennessee, Knoxville, Tennessee 37996, USA.
FAU - Norman, Anthony W
AU  - Norman AW
FAU - Okamura, William H
AU  - Okamura WH
FAU - Sen, Anindita
AU  - Sen A
FAU - Zemel, Michael B
AU  - Zemel MB
LA  - eng
PT  - Journal Article
DEP - 20020905
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (1,25-dihydroxylumisterol(3))
RN  - 0 (DNA, Antisense)
RN  - 0 (Ion Channels)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (UCP2 protein, human)
RN  - 0 (Ucp2 protein, mouse)
RN  - 0 (Uncoupling Protein 2)
RN  - FXC9231JVH (Calcitriol)
RN  - Z30RAY509F (Ergosterol)
SB  - IM
MH  - Adipocytes/cytology/*drug effects/metabolism
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Calcitriol/analogs & derivatives/*pharmacology
MH  - DNA, Antisense/genetics/physiology
MH  - Ergosterol/*analogs & derivatives/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Ion Channels
MH  - *Membrane Transport Proteins
MH  - *Mitochondrial Proteins
MH  - Proteins/*genetics/metabolism
MH  - RNA, Messenger/drug effects/genetics/metabolism
MH  - Receptors, Calcitriol/antagonists & inhibitors/genetics/physiology
MH  - Uncoupling Protein 2
EDAT- 2002/09/12 10:00
MHDA- 2002/12/18 04:00
CRDT- 2002/09/12 10:00
PHST- 2002/09/12 10:00 [pubmed]
PHST- 2002/12/18 04:00 [medline]
PHST- 2002/09/12 10:00 [entrez]
AID - 02-0255fje [pii]
AID - 10.1096/fj.02-0255fje [doi]
PST - ppublish
SO  - FASEB J. 2002 Nov;16(13):1808-10. doi: 10.1096/fj.02-0255fje. Epub 2002 Sep 5.