title: Stimulation of fat storage by prostacyclin and selective agonists of prostanoid IP receptor during the maturation phase of cultured adipocytes.
abstract: We have previously shown that cultured adipocytes have the ability to biosynthesize prostaglandin (PG) I2called alternatively as prostacyclin during the maturation phase by the positive regulation of gene expression of PGI synthase and the prostanoid IP receptor. To clarify how prostacyclin regulates adipogenesis, we investigated the effects of prostacyclin and the specific agonists or antagonists for the IP receptor on the storage of fats during the maturation phase of cultured adipocytes. Exogenous PGI2and the related selective agonists for the IP receptor including MRE-269 and treprostinil rescued the storage of fats attenuated by aspirin, a cyclooxygenase inhibitor. On the other hand, selective antagonists for IP such as CAY10441 and CAY10449 were effective to suppress the accumulation of fats as GW9662, a specific antagonist for peroxisome proliferator-activated receptor (PPAR)γ. Thus, pro-adipogenic action of prostacyclin can be explained by the action mediated through the IP receptor expressed at the maturation stage of adipocytes. Cultured adipocytes incubated with each of PGI2and MRE-269 together with troglitazone, an activator for PPARγ, exhibited additively higher stimulation of fats storage than with either compound alone. The combined effect of MRE-269 and troglitazone was almost abolished by co-incubation with GW9662, but not with CAY10441. Increasing concentrations of troglitazone were found to reverse the inhibitory effect of CAY10441 in a dose-dependent manner while those of MRE-269 failed to rescue adipogenesis suppressed by GW9662, indicating the critical role of the PPARγ activation as a downstream factor for the stimulated adipogenesis through the IP receptor. Treatment of cultured adipocytes with cell permeable stable cAMP analogues or forskolin as a cAMP elevating agent partly restored the inhibitory effect of aspirin. However, excess levels of cAMP stimulated by forskolin attenuated adipogenesis. Supplementation with H-89, a cell permeable inhibitor for protein kinase A (PKA), had no effect on the promoting action of PGI2or MRE-269 along with aspirin on the storage of fats, suggesting that the promotion of adipogenesis mediated by the IP receptor does not require the PKA activity.
authors.affiliation: Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane, 690-8504, Japan.
authors.forename: Ferdous
authors.initials: F
authors.lastname: Khan
authors.affiliation: Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane, 690-8504, Japan.
authors.forename: Pinky Karim
authors.initials: PK
authors.lastname: Syeda
authors.affiliation: Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane, 690-8504, Japan.
authors.forename: Michael Nii N
authors.initials: MN
authors.lastname: Nartey
authors.affiliation: Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane, 690-8504, Japan.
authors.forename: Mohammad Shahidur
authors.initials: MS
authors.lastname: Rahman
authors.affiliation: Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane, 690-8504, Japan.
authors.forename: Mohammad Safiqul
authors.initials: MS
authors.lastname: Islam
authors.affiliation: Department of Molecular and Functional Genomics, Center for Integrated Research in Science, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane, 690-8504, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane, 690-8504, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Jisaka
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima-shi, Tokushima, 7700-8514, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Shono
authors.affiliation: Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane, 690-8504, Japan. yokotaka@life.shimane-u.ac.jp.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Yokota
keywords: 3T3-L1 cells; Adipogenesis; IP receptor; Peroxisome proliferator-activated receptor γ; Prostacyclin; Prostaglandin I2; cAMP