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

Biochem Biophys Res Commun. 2007 Jun 8;357(3):700-6. doi: 10.1016/j.bbrc.2007.03.202. Epub 2007 Apr 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Blotting, Western
  • Cell Differentiation / drug effects
  • Chemokine CCL2 / metabolism
  • Chemokine CCL2 / pharmacology
  • Cyclin D1 / genetics
  • Gene Expression Regulation / drug effects
  • Hypoglycemic Agents / pharmacology
  • Indoleacetic Acids / metabolism
  • Mice
  • Pioglitazone
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Resistin / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Thiazolidinediones / pharmacology
  • Time Factors
  • Transcription Factors / genetics
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Wnt Proteins / physiology*
  • beta Catenin / metabolism

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Hypoglycemic Agents
  • Indoleacetic Acids
  • RNA, Messenger
  • Resistin
  • Thiazolidinediones
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Wnt Proteins
  • beta Catenin
  • Cyclin D1
  • Pioglitazone