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To clarify how anti-adipogenic factors act on preadipocytes to inhibit their differentiation, we compared preadipocyte signaling responses generated by platelet-derived growth factor (PDGF; anti-adipogenic) versus insulin (pro-adipogenic). PDGF, but not insulin, stimulated the phosphorylation of inhibitor of kappaB kinase beta (IKKbeta) in a time-dependent manner. This PDGF-dependent phosphorylation event was inhibited by 60% (P&lt;0.05) when the cells were pretreated with wortmannin, indicating a requirement for the phosphatidylinositol (PI) 3-kinase/AKT pathway. IKKbeta phosphorylation by PDGF was neither accompanied by IkappaBalpha degradation nor NF-kappaB activation. PDGF inhibited human adipocyte differentiation, assessed by triacylglycerol accumulation (75% reduction; P&lt;0.01) and by fatty acid synthase protein expression (60% reduction; P&lt;0.05); these responses were no longer apparent in the presence of sc-514, a selective inhibitor of IKKbeta. Our data describe a novel PDGF response in human preadipocytes that involves the pro-inflammatory kinase IKKbeta and demonstrate that it is required for the inhibition of adipogenesis.

IKKβ and the anti-adipogenic effect of platelet-derived growth factor in human abdominal subcutaneous preadipocytes