Hammarstedt Ann, Isakson Petter, Gustafson Birgit, Smith Ulf
Center of Excellence for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine/Diabetes, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Biochem Biophys Res Commun. 2007 Jun 8;357(3):700-6. doi: 10.1016/j.bbrc.2007.03.202. Epub 2007 Apr 10.
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 TNFalpha 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 TNFalpha 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 TNFalpha on the Wnt-signaling process and, consequently, promote adipogenesis.
2型糖尿病和伴有脂肪细胞增大的肥胖与低度全身炎症、脂肪生成受损以及炎症细胞募集到脂肪组织有关。像肿瘤坏死因子α（TNFα）和白细胞介素6（IL-6）这样的细胞因子由炎症细胞分泌，并且已被证明会损害正常的脂肪细胞分化。这些细胞因子抑制脂肪生成的一个重要机制是维持活跃的Wnt信号通路。此外，像单核细胞趋化蛋白1（MCP-1）和抵抗素这样的其他细胞因子也参与炎症过程，并由巨噬细胞分泌。目前尚不清楚这些细胞因子是否也会影响Wnt信号和脂肪细胞分化。在本研究中，我们发现，虽然TNFα能够维持活跃的Wnt信号、诱导炎症并完全阻断脂肪细胞分化，但MCP-1和抵抗素对这些过程均无影响。噻唑烷二酮类药物吡格列酮的添加被发现可拮抗TNFα对Wnt信号过程的作用，从而促进脂肪生成。
