Complex role of the vitamin D receptor and its ligand in adipogenesis in 3T3-L1 cells.

Published

Journal Article

The vitamin D receptor (VDR) and its ligand 1,25-OH2-VD3 (calcitriol) play an essential role in mineral homeostasis in mammals. Interestingly, the VDR is expressed very early in adipogenesis in 3T3-L1 cells, suggesting that the VDR signaling pathway may play a role in adipocyte biology and function. Indeed, it has been known for a number of years that calcitriol is a potent inhibitor of adipogenesis in this model but with no clear mechanism identified. In this study, we have further defined the molecular mechanism by which the unliganded VDR and calcitriol-liganded VDR regulate adipogenesis. In the presence of calcitriol, the VDR blocks adipogenesis by down-regulating both C/EBPbeta mRNA expression and C/EBPbeta nuclear protein levels at a critical stage of differentiation. In addition, calcitriol allows for the up-regulation of the recently described C/EBPbeta corerepressor, ETO, which would further inhibit the action of any remaining C/EBPbeta, whose action is required for adipogenesis. In contrast, in the absence of calcitriol, the unliganded VDR appears necessary for lipid accumulation, since knock-down of the VDR using siRNA both delays and prevents this process. Taken together, these data support the notion that the intracellular concentrations of calcitriol can play an important role in either promoting or inhibiting adipogenesis via the VDR and the transcriptional pathways that it targets. Further examination of this hypothesis in vivo may shed new light on the biology of adipogenesis.

Full Text

Duke Authors

Cited Authors

  • Blumberg, JM; Tzameli, I; Astapova, I; Lam, FS; Flier, JS; Hollenberg, AN

Published Date

  • April 21, 2006

Published In

Volume / Issue

  • 281 / 16

Start / End Page

  • 11205 - 11213

PubMed ID

  • 16467308

Pubmed Central ID

  • 16467308

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M510343200

Language

  • eng

Conference Location

  • United States