Arachidonic Acid Added during the Differentiation Phase of 3T3-L1 Cells Exerts Anti-Adipogenic Effect by Reducing the Effects of Pro-Adipogenic Prostaglandins

A linoleic acid (LA) metabolite arachidonic acid (AA) added to 3T3-L1 cells is reported to suppress adipogenesis. The purpose of the present study aimed to clarify the effects of AA added during the differentiation phase, including adipogenesis, the types of prostaglandins (PG)s produced, and the crosstalk between AA and the PGs produced. Adipogenesis was inhibited by AA added, while LA did not. When AA was added, increased PGE(2) and PGF(2α) production, unchanged Δ(12)-PGJ(2) production, and reduced PGI(2) production were observed. Since the decreased PGI(2) production was reflected in decreased CCAAT/enhancer-binding protein-β (C/EBPβ) and C/EBPδ expression, we expected that the coexistence of PGI(2) with AA would suppress the anti-adipogenic effects of AA. However, the coexistence of PGI(2) with AA did not attenuate the anti-adipogenic effects of AA. In addition, the results were similar when Δ(12)-PGJ(2) coexisted with AA. Taken together, these results indicated that the metabolism of ingested LA to AA is necessary to inhibit adipogenesis and that exposure of AA to adipocytes during only the differentiation phase is sufficient. As further mechanisms for suppressing adipogenesis, AA was found not only to increase PGE(2) and PGF(2α) and decrease PGI(2) production but also to abrogate the pro-adipogenic effects of PGI(2) and Δ(12)-PGJ(2).