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

Giovanni Solinas, Cristian Vilcu, Jaap G. Neels, Gautam K. Bandyopadhyay, Jun Li Luo, Willscott Naugler, Sergei Grivennikov, Anthony Wynshaw-Boris, Miriam Scadeng, Jerrold M. Olefsky, Michael Karin

Research output: Contribution to journalArticle

393 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)386-397
Number of pages12
JournalCell Metabolism
Volume6
Issue number5
DOIs
StatePublished - Nov 7 2007

Keywords

  • HUMDISEASE
  • SIGNALING

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'JNK1 in Hematopoietically Derived Cells Contributes to Diet-Induced Inflammation and Insulin Resistance without Affecting Obesity'. Together they form a unique fingerprint.

  • Cite this

    Solinas, G., Vilcu, C., Neels, J. G., Bandyopadhyay, G. K., Luo, J. L., Naugler, W., Grivennikov, S., Wynshaw-Boris, A., Scadeng, M., Olefsky, J. M., & Karin, M. (2007). JNK1 in Hematopoietically Derived Cells Contributes to Diet-Induced Inflammation and Insulin Resistance without Affecting Obesity. Cell Metabolism, 6(5), 386-397. https://doi.org/10.1016/j.cmet.2007.09.011