The anti-adipogenic effect of macrophage-conditioned medium requires the IKKβ/NF-κB pathway.

Macrophage-secreted factors inhibit adipogenesis, but the underlying mechanism is not well understood. Our objective was to determine if anti-adipogenic signaling pathways in human preadipocytes are activated by macrophage-conditioned medium (MacCM). Human abdominal subcutaneous stromal preadipocytes were treated with adipogenic inducers in either standard medium or medium conditioned by human THP-1 macrophages. THP-1-MacCM increased inhibitor of κB kinase β (IKKβ) phosphorylation, inhibitor of NF-κB α (IκBα) degradation, and NF-κB activity in human preadipocytes in a time-dependent manner. Concomitant treatment of human abdominal subcutaneous preadipocytes with sc-514, a selective inhibitor of IKKβ, prevented the inhibitory effect of THP-1-MacCM on lipid accumulation and expression of adipogenic markers. Our data indicate that activation of the preadipocyte IKKβ/NF-κB pathway is required for the anti-adipogenic effect of THP-1-MacCM on human adipogenesis. © Georg Thieme Verlag KG Stuttgart · New York.