Vitamin D receptor overexpression promotes differentiation and lipogenesis in 3T3-L1 preadipocytes by increasing peroxisome proliferator-activated receptor gamma expression under vitamin D deficiency.

The core function of the vitamin D receptor (VDR) is to mediate the biological effects of vitamin D and plays an important role in inhibiting adipocyte differentiation. However, previous studies have revealed that VDR has an independent effect-promoting lipogenesis-although the underlying mechanism remains unclear. In this study, we established a 3T3-L1 preadipocyte model overexpressing VDR and treated the cells with the peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 to explore the effects of VDR on adipocyte differentiation and lipogenesis in the absence of vitamin D and to verify the role of PPARγ in this process. Under vitamin D-free conditions, compared with normally induced differentiated cells, 3T3-L1 cells overexpressing VDR presented increased synthesis of fatty acids and triglycerides, elevated expression of PPARγ and its downstream adipogenic regulator C/EBPα, and increased expression of the mature adipocyte marker adiponectin, suggesting that enhanced expression of VDR promotes adipocyte differentiation and lipogenesis. After GW9662 intervention, the expression levels of VDR, PPARγ, C/EBPα, and adiponectin were significantly decreased in both the normal differentiation group and the VDR-overexpressing group. In conclusion, under vitamin D deficiency, increased VDR expression promotes adipocyte differentiation and lipogenesis, and these effects are at least partially mediated by the upregulation of PPARγ expression.