Regulation and role of arachidonate cascade during changes in life cycle of adipocytes

Although some eicosanoids serve as potent natural ligands to activate peroxisome proliferator-activated receptor (PPARγ), the ability of adipocytes to produce eicosanoids and regulate PPARγ remains unclear. Here, adipogenic 3T3-L1 cells were employed to determine the gene expression of isoforms of biosynthetic enzymes in the arachidonate cyclooxygenase (COX) pathway and the synthesis of prostaglandins (PGs). The expression of COX-2 was induced transiently in a biphasic manner upon the triggering of the differentiation and maturation phases while COX-1 was constitutive. The exclusive expression of lipocalin-type PGD synthase occurred and gradually increased during the maturation process along with the stable expression of PPARγ. Moreover, we confirmed the formation of PGD₂ from arachidonic acid by the mature adipocytes, suggesting conversion into PGJ₂ derivatives. Even though cytosolic and membrane-associated subtypes of PGE synthase were expressed at relatively constant levels, the ability of preadipocytes to produce PGE₂ was greater than that of mature adipocytes in the cell response. The treatment of the mature adipocytes with exogenous PGD₂, 15-deoxy-Δ^12,14-PGJ₂ and PGE₂, in the presence of aspirin, enhanced the adipogenesis. These findings imply the specific roles of prostanoids produced by the mature adipocytes in the maintenance of terminal differentiation through an autocrine control mechanism.