Prostanoid EP4 receptor is involved in suppression of 3T3-L1 adipocyte differentiation.
Prostaglandins (PGs) have been shown to play various roles in adipogenesis. In this study, we investigated on which PGE receptor subtypes are involved in the inhibition of 3T3-L1 preadipocyte differentiation. The triglyceride content of cells, used as an index of differentiation, was decreased when PGE(2), the FP-agonist fluprostenol or dibutyryl cAMP, was exogenously added to differentiation cocktails. 3T3-L1 preadipocyte cells express mRNAs for the prostanoid EP4, FP, and IP receptors. PGE(2) and the EP4 agonist AE1-329 increased cAMP levels in preadipocytes in a dose-dependent manner. AE1-329 suppressed the expression induction of differentiation marker genes such as resistin and peroxisome proliferator-activated receptor-gamma. The inhibitory effect of PGE(2) but not that of fluprostenol was reversed by the addition of the EP4 antagonist AE3-208. AE3-208 mimicked the differentiation-promoting effects of indomethacin. These results suggest that the EP4 receptor mediates the suppressive action of PGE(2) in 3T3-L1 adipocyte differentiation.
Tsuboi
Hiroaki
H
Department of Physiological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo-ku, Kyoto 606-8501, Japan.
Sugimoto
Yukihiko
Y
Kainoh
Takayuki
T
Ichikawa
Atsushi
A
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014158:Transcription, Genetic / Q000187:drug effects
D011461:Prostaglandins F, Synthetic; C545651:Ptger4 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; C006326:fluprostenol; D003994:Bucladesine; D015232:Dinoprostone