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¹ Chronic Disease Program, Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9² Departments of Medicine and of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5

(Correspondence should be addressed to A Sorisky; Email: asorisky{at}ohri.ca)

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 B kinase β (IKKβ) 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 pathway. IKKβ phosphorylation by PDGF was neither accompanied by IB degradation nor NF-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 IKKβ. Our data describe a novel PDGF response in human preadipocytes that involves the pro-inflammatory kinase IKKβ and demonstrate that it is required for the inhibition of adipogenesis.