The role of interleukin 1β in the anti-adipogenic action of macrophages on human preadipocytes

When adipose tissue accumulates in obesity, the ability of preadipocytes to differentiate permits a hyperplastic expansion of functional adipocytes that preserves insulin sensitivity. Adipose infiltration by macrophages is associated with an adipogenic deficit and the appearance of inflamed, insulin-resistant hypertrophied adipocytes. Interleukin 1 beta (IL1 beta) has been reported to account for the anti-adipogenic action of macrophages in a mouse model. Using the THP-1 human macrophage cell line and human primary preadipocytes, our objective was to determine whether IL1 beta was necessary for the ability of conditioned medium from THP-1 macrophages (THP-1-MacCM) to: i) stimulate human preadipocyte inhibitor of kappa B kinase beta (IKK beta) and ii) inhibit human adipocyte differentiation. IL1 beta is present in THP-1-MacCM, and THP-1-MacCM or IL1 beta (500 pg/ml; its concentration in THP-1-MacCM) acutely stimulated IKK beta phosphorylation and inhibitor of kappa B (I kappa B) degradation in preadipocytes. IL1 beta was sufficient to inhibit adipogenesis on its own, and this was blocked by SC-514, an IKK beta inhibitor, as has been reported for THP-1-MacCM. I kappa B degradation by IL1 beta-immunodepleted THP-1-MacCM was attenuated, whereas IKK beta phosphorylation and the inhibition of adipocyte differentiation were unchanged. Therefore, in contrast to what has been suggested for mouse cell models, IL1 beta is not required for the ability of MacCM to inhibit adipogenesis in human cell models.