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

Journal of Endocrinology - Tập 201 Số 1 - Trang 75-80 - 2009
AnneMarie Gagnon1, Anne Landry2,3, Alexander Sorisky4
1Chronic Disease Program, Ottawa Health Research Institute, Ottawa, Ontario, Canada
2Chronic Disease Program, Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9
3Departments of Medicine and of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5
4Ottawa Hospital Research Institute

Tóm tắt

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 κB 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 IκBα degradation nor NF-κB 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.

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Journal of Endocrinology

Tập 201 Số 1

75-80

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