Wnt-signaling is maintained and adipogenesis inhibited by TNFα but not MCP-1 and resistin

Type 2 diabetes and obesity with enlarged fat cells are associated with low-grade systemic inflammation, impaired adipogenesis as well as the recruitment of inflammatory cells into the adipose tissue. Cytokines like TNF alpha and IL-6 are secreted by the inflammatory cells and have been shown to impair normal adipocyte differentiation. An important mechanism whereby these cytokines inhibit adipogenesis is by maintaining an active Wnt-signaling pathway. Also other cytokines like MCP-1 and resistin are involved in the inflammatory process and are secreted by macrophages. If these cytokines also affect Wnt-signaling and adipocyte differentiation is currently unclear. In the present study, we show that while TNF alpha is able to maintain an active Wnt-signaling, induce inflammation and completely block adipose cell differentiation, no effect was found by either MCP-1 or resistin on these processes. Addition of the thiazolidinedione, pioglitazone, was found to antagonize the effect of TNF alpha on the Wnt-signaling process and, consequently, promote adipogenesis. (C) 2007 Elsevier Inc. All rights reserved.