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

TY - JOUR

T1 - Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process

AU - Madsen, Lise

AU - Petersen, Rasmus K

AU - Sørensen, Morten B

AU - Jørgensen, Claus

AU - Hallenborg, Philip

AU - Pridal, Lone

AU - Fleckner, Jan

AU - Amri, Ez-Zoubir

AU - Krieg, Peter

AU - Furstenberger, Gerhard

AU - Berge, Rolf K

AU - Kristiansen, Karsten

N1 - 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

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

U2 - 10.1042/BJ20030503

DO - 10.1042/BJ20030503

M3 - Journal article

C2 - 18320708

SN - 0264-6021

VL - 375

SP - 539

EP - 549

JO - Biochemical Journal

JF - Biochemical Journal

IS - Pt 3

ER -