25-Hydroxyvitamin D3 and 1,25-Dihydroxyvitamin D3 Promote the Differentiation of Human Subcutaneous Preadipocytes

Abstract

1,25(OH)2D3 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)D3 to 1,25(OH)2D3, were expressed in human adipose tissues, primary preadipocytes and newly-differentiated adipocytes. Preadipocytes and newly-differentiated adipocytes were responsive to 1,25(OH)2D3, as indicated by a markedly increased expression of CYP24A1, a primary VDR target. 1,25(OH)2D3 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)2D3 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)2D3 promoted maturation. 25(OH)D3 also stimulated CYP24A1 expression and adipogenesis, most likely through its conversion to 1,25(OH)2D3. Consistent with this possibility, incubation of preadipocytes with 25(OH)D3 led to 1,25(OH)2D3 accumulation in the media. 1,25(OH)2D3 also enhanced adipogenesis in primary mouse preadipocytes. We conclude that vitamin D status may regulate human adipose tissue growth and remodeling. © 2012 Nimitphong et al.