Wnt-signaling is maintained and adipogenesis inhibited by TNFalpha 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 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.

Nyckelord

3T3-L1 Cells

Adipocytes/cytology/drug effects/metabolism

Adipogenesis/*drug effects

Animals

Blotting

Western

Cell Differentiation/drug effects

Chemokine CCL2/metabolism/pharmacology

Cyclin D1/genetics

Gene Expression Regulation/drug effects

Hypoglycemic Agents/pharmacology

Indoleacetic Acids/metabolism

Mice

RNA

Messenger/genetics/metabolism

Resistin/pharmacology

Reverse Transcriptase Polymerase Chain Reaction

Signal Transduction/*drug effects/physiology

Thiazolidinediones/pharmacology

Time Factors

Transcription Factors/genetics

Tumor Necrosis Factor-alpha/*pharmacology

Wnt Proteins/*physiology

beta Catenin/metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)