25-hydroxyvitamin D₃ and 1,25-dihydroxyvitamin D₃ promote the differentiation of human subcutaneous preadipocytes

PLoS One. 2012;7(12):e52171. doi: 10.1371/journal.pone.0052171. Epub 2012 Dec 18.

Abstract

1,25(OH)(2)D(3) inhibits adipogenesis in mouse 3T3-L1 adipocytes, but little is known about its effects or local metabolism in human adipose tissue. We showed that vitamin D receptor (VDR) and 1α-hydroxylase (CYP27B1), the enzyme that activates 25(OH)D(3) to 1,25(OH)(2)D(3), were expressed in human adipose tissues, primary preadipocytes and newly-differentiated adipocytes. Preadipocytes and newly-differentiated adipocytes were responsive to 1,25(OH)(2)D(3), as indicated by a markedly increased expression of CYP24A1, a primary VDR target. 1,25(OH)(2)D(3) enhanced adipogenesis as determined by increased expression of adipogenic markers and triglyceride accumulation (50% to 150%). The magnitude of the effect was greater in the absence of thiazolidinediones. 1,25(OH)(2)D(3) was equally effective when added after the removal of differentiation cocktail on day 3, but it had no effect when added only during the induction period (day 0-3), suggesting that 1,25(OH)(2)D(3) promoted maturation. 25(OH)D(3) also stimulated CYP24A1 expression and adipogenesis, most likely through its conversion to 1,25(OH)(2)D(3). Consistent with this possibility, incubation of preadipocytes with 25(OH)D(3) led to 1,25(OH)(2)D(3) accumulation in the media. 1,25(OH)(2)D(3) also enhanced adipogenesis in primary mouse preadipocytes. We conclude that vitamin D status may regulate human adipose tissue growth and remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Adipocytes / cytology*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects
  • Adipogenesis / genetics
  • Adult
  • Animals
  • Calcifediol / pharmacology*
  • Calcitriol / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Mice
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Steroid Hydroxylases / genetics
  • Steroid Hydroxylases / metabolism
  • Subcutaneous Tissue / drug effects*
  • Subcutaneous Tissue / metabolism*
  • Thiazolidinediones / pharmacology
  • Vitamin D3 24-Hydroxylase

Substances

  • Receptors, Calcitriol
  • Thiazolidinediones
  • Steroid Hydroxylases
  • CYP24A1 protein, human
  • Cyp24a1 protein, mouse
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcitriol
  • Calcifediol