Requirement and role of arachidonic acid in the differentiation of pre-adipose cells.
The terminal adipose differentiation of Ob1771 cells, characterized by glycerol-3-phosphate dehydrogenase activity and triacylglycerol accumulation, was studied in serum-free hormone-supplemented medium containing growth hormone, tri-iodothyronine, insulin, transferrin and fetuin. Arachidonic acid was able to substitute for a crude adipogenic fraction isolated from fetal bovine serum but not for growth hormone or tri-iodothyronine. Arachidonic acid was also able to increase in a rapid and dramatic manner cyclic AMP production; moreover it was able to amplify the adipose conversion promoted by other agents elevating cyclic AMP concentrations and to induce inositol phospholipid breakdown. Both phorbol 12-myristate 13-acetate, a protein kinase C activator and ionomycin, a Ca2+-mobilizing agent, showed potent synergy with agents elevating cyclic AMP concentrations for the promotion of adipose conversion, whereas 8-bromo cyclic GMP and 4 alpha-phorbol 12,13-dibutyrate were ineffective. The triggering of both the cyclic AMP and inositol phospholipid pathways was accompanied by a single round of cell division, and within a few days all the cells became differentiated. Similar results were obtained, after exposure to arachidonic acid, with preadipose 3T3-F442A cells and with rat adipose precursor cells in primary culture. The availability of arachidonic acid from intracellular stores and/or of exogenous origin should play a major role for the onset of critical mitoses leading to terminal differentiation in pre-adipose cells.
Gaillard
D
D
Laboratoire de Biologie du Développment du Tissu Adipeux, Centre de Biochimie du C.N.R.S., (L.P. 7300), Faculté des Sciences, Nice, France.
Négrel
R
R
Lagarde
M
M
Ailhaud
G
G
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism; D004987:Ethers / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D015759:Ionomycin; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
D001095:Arachidonic Acids; D004987:Ethers; D010743:Phospholipids; D016718:Arachidonic Acid; C016276:8-bromocyclic GMP; D015240:Phorbol 12,13-Dibutyrate; D007294:Inositol; D015759:Ionomycin; D000242:Cyclic AMP; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate