Prostacyclin as a potent effector of adipose-cell differentiation.
The terminal differentiation of Ob1771 pre-adipose cells induced by arachidonic acid in serum-free hormone-supplemented medium containing insulin, transferrin, growth hormone, tri-iodothyronine and fetuin (5F medium) was strongly diminished in the presence of inhibitors of prostaglandin synthesis, namely aspirin or indomethacin. Carbaprostacyclin, a stable analogue of prostacyclin (prostaglandin I2) known to be synthesized by pre-adipocytes and adipocytes, behaved as an efficient activator of cyclic AMP production and was able, when added to 5F medium, to mimic the adipogenic effect of arachidonic acid. Prostaglandins E2, F2 alpha and D2, unable to affect the cyclic AMP production, failed to substitute for carbaprostacyclin. However, prostaglandin F2 alpha, which is another metabolite of arachidonic acid in pre-adipose and adipose cells, able to promote inositol phospholipid breakdown and protein kinase C activation, potentiated the adipogenic effect of carbaprostacyclin. In addition, carbaprostacyclin enhanced both a limited proliferation and terminal differentiation of adipose precursor cells isolated from rodent and human adipose tissues maintained in primary culture. These results demonstrate the critical role of prostacyclin and prostaglandin F2 alpha on adipose conversion in vitro and suggest a paracrine/autocrine role of both prostanoids in the development of adipose tissue in vivo.
Négrel
R
R
Laboratoire de Biologie du Développement du Tissu Adipeux, Centre de Biochimie du C.N.R.S. (L.P. 7300), Faculté des Sciences, Nice, France.
Gaillard
D
D
Ailhaud
G
G
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D011464:Epoprostenol / Q000378:metabolism* / Q000031:analogs & derivatives; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D008938:Mitosis; D011460:Prostaglandins F / Q000378:metabolism; D011465:Prostaglandins, Synthetic / Q000378:metabolism; D051381:Rats
D001095:Arachidonic Acids; D011460:Prostaglandins F; D011465:Prostaglandins, Synthetic; D016718:Arachidonic Acid; C026678:carboprostacyclin; D011464:Epoprostenol; D000242:Cyclic AMP; D001241:Aspirin; D007213:Indomethacin