Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process

Research output: Contribution to journalJournal articleResearchpeer-review

  • Madsen, Lise
  • Rasmus K Petersen
  • Morten B Sørensen
  • Claus Jørgensen
  • Philip Hallenborg
  • Lone Pridal
  • Jan Fleckner
  • Ez-Zoubir Amri
  • Peter Krieg
  • Gerhard Furstenberger
  • Rolf K Berge
  • Kristiansen, Karsten
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.
Original languageEnglish
JournalBiochemical Journal
Volume375
Issue numberPt 3
Pages (from-to)539-49
Number of pages10
ISSN0264-6021
DOIs
Publication statusPublished - 2003

Bibliographical note

Keywords: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Arachidonate 12-Lipoxygenase; Arachidonate 15-Lipoxygenase; Dose-Response Relationship, Drug; Flavanones; Ligands; Lipoxygenase; Lipoxygenase Inhibitors; Mice; Nordihydroguaiaretic Acid; PPAR gamma; Thiazolidinediones; Time Factors; Transcriptional Activation

ID: 21338344