J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M300248-JLR200 on July 1, 2003

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Journal of Lipid Research, Vol. 44, 1652-1659, September 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Selective cyclo-oxygenase-2 inhibitors impair adipocyte differentiation through inhibition of the clonal expansion phase

Lluis Fajas1,*, Stéphanie Miard*, Michael R. Briggs{dagger} and Johan Auwerx2,*

* Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B. P. 163, F-67404 Illkirch cedex, C.U. de Strasbourg, France
{dagger} Pharmacia Discovery Research, St. Louis, MO 63198

2 To whom correspondence should be addressed. e-mail: auwerx{at}igbmc.u-strasbg.fr

Selective cyclo-oxygenase-2 (COX-2) inhibitors are nonsteroidal antiinflammatory drugs used in the management of inflammatory diseases. We demonstrate here that inhibition of the COX-2 enzyme impairs adipocyte differentiation. The inhibition of adipogenesis occurs in the early clonal expansion phase. In particular, COX-2 inhibition limits cell cycle reentry required before terminal adipocyte differentiation. This inhibition of adipogenesis is independent of the production of the peroxisome proliferator activated receptor {gamma} ligand prostaglandin J2, but dependent on the production of proliferative prostaglandins, such as prostaglandin E2.

Modulation of the activity of the COX-2 enzyme via COX-2 selective inhibitors might open up new perspectives in the control of obesity and related metabolic diseases.

Supplementary key words peroxisome proliferator activated receptor {gamma} • cell cycle • insulin resistance • obesity


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