JNK1 in Hematopoietically Derived Cells Contributes to Diet-Induced Inflammation and Insulin Resistance without Affecting Obesity

Obesity-induced insulin resistance is a major factor in the etiology of type 2 diabetes, and Jun kinases (JNKs) are key negative regulators of insulin sensitivity in the obese state. Activation of JNKs (mainly JNK1) in insulin target cells results in phosphorylation of insulin receptor substrates (I...

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Bibliographic Details
Published in:Cell metabolism 2007-11, Vol.6 (5), p.386-397
Main Authors: Solinas, Giovanni, Vilcu, Cristian, Neels, Jaap G., Bandyopadhyay, Gautam K., Luo, Jun-Li, Naugler, Willscott, Grivennikov, Sergei, Wynshaw-Boris, Anthony, Scadeng, Miriam, Olefsky, Jerrold M., Karin, Michael
Format: Article
Language:English
Subjects:
Animals
Basic Medicine
Cells, Cultured
Cytokines - metabolism
Dietary Fats - administration & dosage
Energy Metabolism
Flow Cytometry
Hematopoietic Stem Cells - enzymology
Hematopoietic Stem Cells - metabolism
HUMDISEASE
inflammation
Inflammation - chemically induced
Inflammation - metabolism
Inflammation - physiopathology
Insulin Resistance
Interleukin-6 - metabolism
JNK
JNK Mitogen-Activated Protein Kinases - genetics
JNK Mitogen-Activated Protein Kinases - metabolism
Macrophages - cytology
Macrophages - drug effects
Macrophages - metabolism
Magnetic Resonance Imaging
Medicinska grundvetenskaper
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Biological
obesity
Obesity - chemically induced
Obesity - metabolism
Obesity - physiopathology
Palmitates - pharmacology
SIGNALING
Tumor Necrosis Factor-alpha - metabolism
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Summary:Obesity-induced insulin resistance is a major factor in the etiology of type 2 diabetes, and Jun kinases (JNKs) are key negative regulators of insulin sensitivity in the obese state. Activation of JNKs (mainly JNK1) in insulin target cells results in phosphorylation of insulin receptor substrates (IRSs) at serine and threonine residues that inhibit insulin signaling. JNK1 activation is also required for accumulation of visceral fat. Here we used reciprocal adoptive transfer experiments to determine whether JNK1 in myeloid cells, such as macrophages, also contributes to insulin resistance and central adiposity. Our results show that deletion of Jnk1 in the nonhematopoietic compartment protects mice from high-fat diet (HFD)-induced insulin resistance, in part through decreased adiposity. By contrast, Jnk1 removal from hematopoietic cells has no effect on adiposity but confers protection against HFD-induced insulin resistance by decreasing obesity-induced inflammation.
ISSN:1550-4131
1932-7420
1932-7420
DOI:10.1016/j.cmet.2007.09.011