Suppression of adipogenesis program in cultured preadipocytes transfected stably with cyclooxygenase isoforms

  • Chu X
  • Xu L
  • Nishimura K
 et al. 
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Prostaglandins (PGs) are known to play a variety of roles in adipocytes and precursor cells, which have the arachidonate cyclooxygenase (COX) pathway to generate several series of PGs at different stages of life cycle of adipocytes. To gain a unique insight into the specific roles of the COX isoforms during the life cycle of adipocytes, 3T3-L1 preadipocytes were stably transfected with a mammalian expression vector harboring either cDNA coding for murine COX-1 or COX-2. The cloned stable transfectants with COX-1 or COX-2 exhibited higher expression levels of their corresponding mRNA and proteins, and greater production of PGE2upon stimulation with free arachidonic acid or A23187 than the parent cells and the transfectants with vector only. However, either type of transfectants brought about the marked reduction in the accumulation of triacylglycerols after the standard adipogenesis program. Unexpectedly, aspirin or other COX inhibitors at different phases of life cycle of adipocytes failed to reverse the reduced storage of fats. The transfectants with COX-2 were sensitive to exogenous 15-deoxy-Δ12,14-PGJ2(15d-PGJ2) and troglitazone as peroxisome proliferator-activated receptor γ (PPARγ) agonists during the maturation phase for restoring the adipogenesis. By contrast, the transfectants with COX-1 were much less sensitive, which was reflected by much lower gene expression levels of PPARγ and the related adipocyte-specific markers. Taken together, the results suggest that the sustained overexpression of either COX-1 or COX-2 resulted in the interference of adipogenesis program through a PG-independent mechanism with a different mode of action of COX isoforms. © 2009 Elsevier B.V. All rights reserved.

Author-supplied keywords

  • 3T3-L1 cell
  • Adipocyte
  • Cyclooxygenase
  • Overexpression
  • Prostanoid
  • Stable transfection

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  • Xiaoqing Chu

  • Li Xu

  • Kohji Nishimura

  • Mitsuo Jisaka

  • Tsutomu Nagaya

  • Fumiaki Shono

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