Modulation of the expression of sphingosine 1-phosphate 2 receptors regulates the differentiation of pre-adipocytes

Abstract

Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator that regulates multiple signals through S1P receptors responsible for biological responses. In particular, the S1P2 receptor has distinct roles in the S1P-mediated differentiation of certain cell types. The present study was the first, to the best of our knowledge, to report the role of the S1P2 receptor in the adipocyte differentiation of 3T3-L1 pre-adipocytes. In order to investigate the influence of S1P2 receptors in the anti-adipogenic effects of S1P, S1P2 receptor silencing and overexpression of were used. S1P2 overexpression with adenoviral vectors inhibited adipogenesis and inhibited the expression of peroxisome proliferator-activated receptor γ (PPARγ), adiponectin and CCAAT/enhancer binding protein-α, which were upregulated following incubation in differentiation media. Furthermore, S1P completely lost its ability to impair adipogenic differentiation following silencing of S1P2. Silencing of the S1P2 receptor additionally blocked the downregulation of PPARγ protein and phospho-c-Jun N-terminal kinase protein induced by S1P treatment. In conclusion, the present study demonstrated that the S1P2 receptor is a key signaling molecule in the S1P-dependent inhibition of adipogenic differentiation and additionally suggested that selective targeting of S1P2 receptors may have clinical applications for the treatment of obesity.