Activation of S1P2 receptor, a possible mechanism of inhibition of adipogenic differentiation by sphingosine 1phosphate

Sphingosine 1phosphate (S1P) belongs to a significant group of signaling sphingolipids and exerts most of its activity as a ligand of Gproteincoupled receptors. In our previous study, S1P demonstrated a novel biological activity with the antiadipogenesis of 3T3L1 preadipocytes. In the present study, we identified a possible mechanism of S1Pmediated antiadipogenic effects, particularly in target pathways of the S1P receptors, including S1P₁ and S1P₂. The mRNA levels of S1P₁ and S1P₂ receptors were increased by MDI media treatment, whereas S1P treatment highly induced S1P₂ but not S1P₁ receptor protein in adipocytes. Triglyceride accumulation assay using an agonist and antagonist of S1P receptors revealed that S1P₂ receptor was only involved in S1Pmediated antiadipogenic effects. Furthermore, pharmacological inhibition of S1P₂ signals completely retrieved S1Pmediated downregulation of the transcriptional levels of peroxisome proliferatoractivated receptor γ, CCAAT/enhancer binding protein α and adiponectin, which are markers of adipogenic differentiation. This study demonstrated that S1P₂ receptor signals may regulate the S1Pmediated antiadipogenic differentiation and also identifies the S1P₂ receptor as a possible mechanism of antiadipogenic differentiation.