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Cell Biology Commons

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Physiology

2012

3T3 Cells; Adipocytes; Animals; Cell Communication; Coculture Techniques; Cytokines; Humans; Insulin; Insulin Resistance; JNK Mitogen-Activated Protein Kinases; Macrophage Activation; Macrophages; Membrane Proteins; Mice; Retinol-Binding Proteins, Plasma; Signal Transduction; Toll-Like Receptor 4; Vitamin A

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Full-Text Articles in Cell Biology

Retinol-Binding Protein 4 Inhibits Insulin Signaling In Adipocytes By Inducing Proinflammatory Cytokines In Macrophages Through A C-Jun N-Terminal Kinase- And Toll-Like Receptor 4-Dependent And Retinol-Independent Mechanism, Julie Norseen, Tetsuya Hosooka, Ann Hammarstedt, Mark M. Yore, Shashi Kant, Pratik Aryal, Urban A. Kiernan, David A. Phillips, Hiroshi Maruyama, Bettina J. Kraus, Anny Usheva, Roger J. Davis, Ulf Smith, Barbara B. Kahn May 2012

Retinol-Binding Protein 4 Inhibits Insulin Signaling In Adipocytes By Inducing Proinflammatory Cytokines In Macrophages Through A C-Jun N-Terminal Kinase- And Toll-Like Receptor 4-Dependent And Retinol-Independent Mechanism, Julie Norseen, Tetsuya Hosooka, Ann Hammarstedt, Mark M. Yore, Shashi Kant, Pratik Aryal, Urban A. Kiernan, David A. Phillips, Hiroshi Maruyama, Bettina J. Kraus, Anny Usheva, Roger J. Davis, Ulf Smith, Barbara B. Kahn

Davis Lab Publications

Retinol-binding protein 4 (RBP4), the sole retinol transporter in blood, is secreted from adipocytes and liver. Serum RBP4 levels correlate highly with insulin resistance, other metabolic syndrome factors, and cardiovascular disease. Elevated serum RBP4 causes insulin resistance, but the molecular mechanisms are unknown. Here we show that RBP4 induces expression of proinflammatory cytokines in mouse and human macrophages and thereby indirectly inhibits insulin signaling in cocultured adipocytes. This occurs through activation of c-Jun N-terminal protein kinase (JNK) and Toll-like receptor 4 (TLR4) pathways independent of the RBP4 receptor, STRA6. RBP4 effects are markedly attenuated in JNK1-/- JNK2-/- macrophages and TLR4- ...