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.
Highlights
In addition to its roles in regulating systemic calcium homeostasis and skeletal health, 1,25-dihydroxyvitamin D [1,25(OH)2D, D represents D2 or D3] regulates differentiation, proliferation and apoptosis of many cells types [1,2]
Previous studies demonstrated that vitamin D receptor (VDR) is expressed in human Simpson–Golabi–Behmel syndrome (SGBS) preadipocytes and adipocytes [8] and that 1a-hydroxylase is expressed in 3T3-L1 fibroblasts and rodent adipose tissues [9], but no data are available on intact human adipose tissue and its cellular constituents
To determine whether human preadipocytes and adipocytes respond to 1,25(OH)2D3, we tested whether it increased the expression of a known vitamin D target gene, CYP24A1. 1,25(OH)2D3 markedly increased CYP24A1 mRNA in both human preadipocytes and newly-differentiated adipocytes (Fig. 2)
Summary
In addition to its roles in regulating systemic calcium homeostasis and skeletal health, 1,25-dihydroxyvitamin D [1,25(OH)2D, D represents D2 or D3] regulates differentiation, proliferation and apoptosis of many cells types [1,2]. As the relevance of cultured mouse cell lines to human physiology is not known, we embarked on studies of 1,25(OH)2D3 action on the differentiation of primary human preadipocytes. The local production of 1,25(OH)2D from 25-hydroxyvitamin D [25(OH)D], catalyzed by 1a-hydroxylase (CYP27B1), modulates the cell and tissue specific regulation of this hormone’s action [6,7]. Previous studies demonstrated that VDR is expressed in human Simpson–Golabi–Behmel syndrome (SGBS) preadipocytes and adipocytes [8] and that 1a-hydroxylase is expressed in 3T3-L1 fibroblasts and rodent adipose tissues [9], but no data are available on intact human adipose tissue and its cellular constituents
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
