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.
Hammarstedt
Ann
A
Center of Excellence for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine/Diabetes, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. ann.hammarstedt@medic.gu.se
Isakson
Petter
P
Gustafson
Birgit
B
Smith
Ulf
U
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism / Q000494:pharmacology; D019938:Cyclin D1 / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007210:Indoleacetic Acids / Q000378:metabolism; D051379:Mice; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D052243:Resistin / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007004:Hypoglycemic Agents; D007210:Indoleacetic Acids; D012333:RNA, Messenger; D052243:Resistin; D045162:Thiazolidinediones; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; D000077205:Pioglitazone