Interactive Pro-Adipogenic Effect of 15-deoxy-Δ12,14-Prostaglandin J2 to Interfere the Inducible Synthesis of Anti-Adipogenic Prostanoids in Cultured 3T3-L1 Preadipocytes, an Important Molecular Event to Consider for Drug Development

摘要

Adipocytes in animal adipose tissues are always affected by a variety of mitogenic and inflammatory factors in autocrine andparacrine manners. Prostanoids generated from these adipocytes at different life stages could exert their interactive effects onthe arachidonate cyclooxygenase (COX) pathway in adipose tissues. Many drug candidates from natural sources have alreadybeen evaluated to explore the molecular interaction with COX pathway. The present study was undertaken to explore theinteracting effects of 15-deoxyΔ12,14-prostaglandin J2 (15d-PGJ2) on the inducible biosynthesis of PGE2 and PGF2α" by cultured 3T3-L1 preadipocytes during the growth phase as a model system. We found that the synthesis of the anti-adipogenicprostanoids by preadipocytes was significantly suppressed by the co-incubation with 15d-PGJ2 due to the reduced induction ofCOX-2 following the interference of NF-κB pathway. Our study also revealed that 15d-PGJ2 was able to rescue the inhibitoryeffects of endogenous prostaglandins synthesized in preadipocytes during the growth phase. The revealed molecularphenomena might provide important information for treating obesity related disorders by developing new drugs from naturalsources.