Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process
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Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process. / Madsen, Lise; Petersen, Rasmus K; Sørensen, Morten B; Jørgensen, Claus; Hallenborg, Philip; Pridal, Lone; Fleckner, Jan; Amri, Ez-Zoubir; Krieg, Peter; Furstenberger, Gerhard; Berge, Rolf K; Kristiansen, Karsten.
In: Biochemical Journal, Vol. 375, No. Pt 3, 2003, p. 539-49.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 375
SP - 539
EP - 549
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - Pt 3
ER -
ID: 21338344