Sphingosine-1-phosphate inhibits the adipogenic differentiation of 3T3-L1 preadipocytes

Sphingosine-l-phosphate (S1P) is a pluripotent lipid mediator that transmits signals through G-protein-coupled receptors to control diverse biological processes. The novel biological activity of SIP in the adipogenesis of 3T3-L1 preadipocytes was identified in the present study. SIP significantly decreased lipid accumulation in maturing preadipocytes in a dose-dependent manner. In order to understand the anti-adipogenic effects of S1P, preadipocytes were treated with SIP, and the change in the expression of several adipogenic transcription factors and enzymes was investigated using quantitative RT-PCR. S1P downregulated the transcriptional levels of the peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding proteins and adiponectin, which are markers of adipogenic differentiation. The effects of SIP on the levels of mitogen-activated protein kinase (MAPK) signals in preadipocytes were also investigated. The activation of JNK and p38 were downregulated by S1P treatment in human preadipocytes. In conclusion, the results of this study suggest that SIP alters fat mass by directly affecting adipogenesis. This is mediated by the downregulation of adipogenic transcription factors and by inactivation of the JNK and p38 MAPK pathways. Thus, selective targeting of the SIP receptors and sphingosine kinases may have clinical applications for the treatment of obesity.