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

Biochem J. 2003 Nov 1;375(Pt 3):539-49. doi: 10.1042/bj20030503.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology*
  • Adipocytes / drug effects
  • Adipocytes / enzymology
  • Adipogenesis* / drug effects
  • Adipose Tissue, Brown / enzymology
  • Adipose Tissue, White / enzymology
  • Animals
  • Arachidonate 12-Lipoxygenase / metabolism
  • Arachidonate 15-Lipoxygenase / metabolism
  • Dose-Response Relationship, Drug
  • Flavanones / pharmacology
  • Ligands
  • Lipoxygenase / genetics
  • Lipoxygenase / metabolism*
  • Lipoxygenase Inhibitors / pharmacology
  • Masoprocol / pharmacology
  • Mice
  • PPAR gamma / agonists
  • PPAR gamma / metabolism
  • Rosiglitazone
  • Thiazolidinediones / pharmacology
  • Time Factors
  • Transcriptional Activation / drug effects

Substances

  • 12-15-lipoxygenase
  • Flavanones
  • Ligands
  • Lipoxygenase Inhibitors
  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone
  • baicalein
  • Masoprocol
  • Lipoxygenase
  • eLOX3 protein, mouse
  • Arachidonate 12-Lipoxygenase
  • Arachidonate 15-Lipoxygenase