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

Sphingosine 1‑phosphate (S1P) belongs to a significant group of signaling sphingolipids and exerts most of its activity as a ligand of G‑protein‑coupled receptors. In our previous study, S1P demonstrated a novel biological activity with the anti‑adipogenesis of 3T3‑L1 preadipocytes. In the present study, we identified a possible mechanism of S1P‑mediated anti‑adipogenic 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 S1P‑mediated anti‑adipogenic effects. Furthermore, pharmacological inhibition of S1P2 signals completely retrieved S1P‑mediated downregulation of the transcriptional levels of peroxisome proliferator‑activated 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 S1P‑mediated anti‑adipogenic differentiation and also identifies the S1P2 receptor as a possible mechanism of anti‑adipogenic differentiation.