TNFalpha is a potent inducer of platelet-activating factor synthesis in adipocytes but not in preadipocytes. Differential regulation by PI3K.
Tumour necrosis factor alpha (TNFalpha) induces platelet-activating factor (PAF) synthesis in many inflammatory cells. Here, we investigate the possibility that TNFalpha stimulates PAF synthesis in rat adipocytes and preadipocytes and that phosphoinositide 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) are implicated in this process. Primary cultures were incubated with [3H]lyso-PAF and stimulated by TNFalpha in the presence or absence of wortmannin. We found that, although both cultures synthesized PAF at a similar basal rate, TNFalpha-induced PAF synthesis in adipocytes was 7-fold higher than in preadipocytes. This suggested a maturation of PAF-TNFalpha interrelationship during adipocyte differentiation. Wortmannin enhanced TNFalpha-dependent PAF synthesis in adipocytes but not in preadipocytes, indicating the negative control by PI3K in mature cells. PAF increase was due to the regulation of its biosynthesis since PAF-acetylhydrolase (PAF-AH) activity was TNFalpha- and wortmannin-independent. Our hypothesis is that PAF mediates TNFalpha inflammatory effects in both adipocytes and preadipocytes and that this pathway is enhanced during adipocyte differentiation, a mechanism which is highly active during the development of obesity.
Gountopoulou
Alexandra
A
Laboratory of Biochemistry, Department of Chemistry, University of Athens, Zografou, 15771 Athens, Greece.
Leondaritis
George
G
Galanopoulou
Dia
D
Mavri-Vavayanni
Mary
M
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000077191:Wortmannin
D000730:Androstadienes; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000077191:Wortmannin