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

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 kappa B kinase beta (IKK beta) in a time-dependent manner. This PDGF-dependent phosphorylation event was inhibited by 60% (P < 0.05) when the cells were pretreated with wortmannin, indicating a requirement for the phosphatidylinositol (PI) 3-kinase/AKT pathways IKK beta phosphorylation by PDGF was neither accompanied by IKB alpha degradation nor NF-kappa B activation. PDGF inhibited human adipocyte differentiation, assessed by triacylglycerol accumulation (75% reduction; P < 0.01) and by fatty acid synthase protein expression (60% reduction; P < 0.05); these responses were no longer apparent in the presence of sc-514, a selective inhibitor of IKK beta. Our data describe a novel PDGF response in human preadipocytes that involves the pro-inflammatory kinase IKK beta and demonstrate that it is required for the inhibition of adipogenesis. Journal of Endocrinology (2009) 201, 75-80