Original Article
International Journal of Obesity advance online publication 22 April 2008; doi: 10.1038/ijo.2008.59
1
, 25-Dihydroxyvitamin D and corticosteroid regulate adipocyte nuclear vitamin D receptor
1Department of Nutrition, University of Tennessee, Knoxville, TN, USA
Correspondence: Dr MB Zemel, Department of Nutrition, University of Tennessee, 1215 West Cumberland Avenue, no. 229, Knoxville, TN 37996-1900, USA. E-mail: mzemel@utk.edu
Received 13 January 2008; Revised 18 February 2008; Accepted 19 March 2008; Published online 22 April 2008.
Abstract
Objective:
We previously demonstrated that high calcium diets inhibit obesity in both mice and humans; this effect is mediated, in part, by dietary calcium suppression of 1
, 25-dihydroxyvitamin D, which exerts both non-genomic and genomic effects on adipocyte metabolism. However, the presence of the nuclear vitamin D receptor (nVDR) and its role in this regulation in adipocytes have not been investigated.
Methods and results:
The nVDR is expressed at low levels in preadipocytes, and differentiation induced a rapid 1150%
increase within 3 h (P<0.001), which then declined rapidly to preadipocyte levels at differentiation day 3. However, this was not a differentiation event, as the components of the differentiation mixture (isobutylmethylxanthine and dexamethasone) also increased nVDR expression markedly by 1620 and 284%
, respectively, in fully differentiated adipocytes (P<0.05). 1, 25-Dihydroxyvitamin D and 11
-dehydrocorticosterone each stimulated nVDR expression at 48 h, but not 3 h, by 
650%
in fully differentiated adipocytes, whereas the combination augmented this effect (P<0.005). Knockdown of 11-hydroxysteroid dehydrogenase I (11-HSD I) markedly decreased adipocyte nVDR expression and attenuated 1, 25-dihydroxyvitamin D stimulation of nVDR. Thus, 1, 25-dihydroxyvitamin D stimulation of corticosteroid synthesis via the 11-HSD appears to provide an indirect positive feedback on the nVDR. 1, 25-Dihydroxyvitamin D also regulated short-term corticosterone release independently of either 11-HSD I or nVDR. Knockdown 11-HSD I did not affect short-term corticosterone release, whereas modulating calcium influx by KCl, BAYK8644 and the membrane 1, 25-dihydroxyvitamin D receptor agonist lumisterol markedly increased corticosterone release.
Conclusion:
These data suggest a potential role of nVDR and corticosterone in the regulation in adipocyte responses to 1, 25-dihydroxyvitamin D and dietary calcium.
Keywords:
1, 25-dihydroxyvitamin D, corticosteroid, nVDR, adipocyte
