title: Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process.
abstract: Adipocytes play a central role in whole-body energy homoeostasis. Complex regulatory transcriptional networks control adipogensis, with ligand-dependent activation of PPARgamma (peroxisome proliferator-activated receptor gamma) being a decisive factor. Yet the identity of endogenous ligands promoting adipocyte differentiation has not been established. Here we present a critical evaluation of the role of LOXs (lipoxygenases) during adipocyte differentiation of 3T3-L1 cells. We show that adipocyte differentiation of 3T3-L1 preadipocytes is inhibited by the general LOX inhibitor NDGA (nordihydroguaiaretic acid) and the 12/15-LOX selective inhibitor baicalein. Baicalein-mediated inhibition of adipocyte differentiation was rescued by administration of rosiglitazone. Treatment with baicalein during the first 4 days of the differentiation process prevented adipocyte differentiation; supplementation with rosiglitazone during the same period was sufficient to rescue adipogenesis. Accordingly, we demonstrate that adipogenic conversion of 3T3-L1 cells requires PPARgamma ligands only during the first 4 days of the differentiation process. We show that the baicalein-sensitive synthesis of endogenous PPARgamma ligand(s) increases rapidly upon induction of differentiation and reaches a maximum on days 3-4 of the adipocyte differentiation programme. The conventional platelet- and leucocyte-type 12(S)-LOXs and the novel eLOX-3 (epidermis-type LOX-3) are expressed in white and brown adipose tissue, whereas only eLOX-3 is clearly expressed in 3T3-L1 cells. We suggest that endogenous PPARgamma ligand(s) promoting adipocyte differentiation are generated via a baicalein-sensitive pathway involving the novel eLOX-3.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Madsen
authors.forename: Rasmus K
authors.initials: RK
authors.lastname: Petersen
authors.forename: Morten B
authors.initials: MB
authors.lastname: Sørensen
authors.forename: Claus
authors.initials: C
authors.lastname: Jørgensen
authors.forename: Philip
authors.initials: P
authors.lastname: Hallenborg
authors.forename: Lone
authors.initials: L
authors.lastname: Pridal
authors.forename: Jan
authors.initials: J
authors.lastname: Fleckner
authors.forename: Ez-Zoubir
authors.initials: EZ
authors.lastname: Amri
authors.forename: Peter
authors.initials: P
authors.lastname: Krieg
authors.forename: Gerhard
authors.initials: G
authors.lastname: Furstenberger
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Berge
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D050156:Adipogenesis / Q000187:drug effects; D002001:Adipose Tissue, Brown / Q000201:enzymology; D052436:Adipose Tissue, White / Q000201:enzymology; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology; D008024:Ligands; D008084:Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: C475064:12-15-lipoxygenase; D044950:Flavanones; D008024:Ligands; D016859:Lipoxygenase Inhibitors; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C006680:baicalein; D009637:Masoprocol; D008084:Lipoxygenase; C518403:eLOX3 protein, mouse; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase