1,25-Dihydroxyvitamin D3 modulates adipogenesis of human adipose-derived mesenchymal stem cells dose-dependently

1,25-dihydroxyvitamin D3 may regulate adipogenesis in adipocytes in-vitro, but little is known about possible molecular mechanisms related to the inhibitory effect of 1,25-dihydroxyvitamin D3 on adipogenesis in humans҆ adipose tissue.

In this study, human adipose-derived mesenchymal stem cells (hASCs) were cultured for 14 days in adipogenic differentiation media containing concentrations of 1,25-dihydroxyvitamin D3 (10^-10-10^-8 M). The extent of adipogenic differentiation in ASCs was assessed by Oil Red O staining and quantitative polymerase chain reaction (PCR) to determine expression levels of key adipogenic markers.

Our results showed that vitamin D receptor (VDR), as a mediator of most actions of 1,25-dihydroxyvitamin D3, glucose trasporter-4 (GLUT4),and fatty acid binding protein-4 (FABP4) was expressed in vitamin D-treated hASCs. However, the protein level of these markers was lower than the control group. Treatment of human preadipocytes with 1,25-dihydroxyvitamin D3 significantly altered expression of adipogenic markers and triglyceride accumulation in a dose-dependent manner. 1,25-dihydroxyvitamin D3 at concentration of 10^-8 M enhanced expression of sterol regulatory element-binding protein-1c (SREBP1c), CCAAT-enhancer-binding protein-β (C/EBPβ), a mitotic clonal expansion, peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FASN), a marker of de novo lipogenesis,and lipoprotein lipase (LPL).

Our findings revealed that 1,25-dihydroxyvitamin D3 may provoke adipocyte development in critical periods of adipogenesis at concentration of 10^-8 M, thereby leading to a greater risk of obesity in adulthood and an augmented risk of obesity-related diseases including diabetes, cardiovascular diseases, and some cancers.