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.