title: Arachidonic acid-dependent gene regulation during preadipocyte differentiation controls adipocyte potential.
abstract: Arachidonic acid (AA) is a major PUFA that has been implicated in the regulation of adipogenesis. We examined the effect of a short exposure to AA at different stages of 3T3-L1 adipocyte differentiation. AA caused the upregulation of fatty acid binding protein 4 (FABP4/aP2) following 24 h of differentiation. This was mediated by the prostaglandin F(2α) (PGF(2α)), as inhibition of cyclooxygenases or PGF(2α) receptor signaling counteracted the AA-mediated aP2 induction. In addition, calcium, protein kinase C, and ERK are all key elements of the pathway through which AA induces the expression of aP2. We also show that treatment with AA during the first 24 h of differentiation upregulates the expression of the transcription factor Fos-related antigen 1 (Fra-1) via the same pathway. Finally, treatment with AA for 24 h at the beginning of the adipocyte differentiation is sufficient to inhibit the late stages of adipogenesis through a Fra-1-dependent pathway, as Fra-1 knockdown rescued adipogenesis. Our data show that AA is able to program the differentiation potential of preadipocytes by regulating gene expression at the early stages of adipogenesis.
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Evanthia
authors.initials: E
authors.lastname: Nikolopoulou
authors.affiliation: Division of Women's Health, King's College London, London, UK.
authors.forename: Georgia
authors.initials: G
authors.lastname: Papacleovoulou
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Frederic
authors.initials: F
authors.lastname: Jean-Alphonse
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Giulia
authors.initials: G
authors.lastname: Grimaldi
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Parker
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Aylin C
authors.initials: AC
authors.lastname: Hanyaloglu
authors.affiliation: Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Christian
mesh_terms: D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D020013:Calcium Signaling; D015237:Dinoprost / Q000378:metabolism; D015536:Down-Regulation; D050556:Fatty Acid-Binding Proteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007700:Kinetics; D020935:MAP Kinase Signaling System; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D011982:Receptors, Prostaglandin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D000099169:Fos-Related Antigen 1
chemical_list: D016718:Arachidonic Acid; D015237:Dinoprost; D050556:Fatty Acid-Binding Proteins; D011493:Protein Kinase C; D016760:Proto-Oncogene Proteins c-fos; D034741:RNA, Small Interfering; D011982:Receptors, Prostaglandin; D000099169:Fos-Related Antigen 1; C493411:Fabp4 protein, mouse; C034671:prostaglandin F2alpha receptor
keywords: adipogenesis; cell signaling; metabolism; prostaglandins