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 (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.
Solinas
Giovanni
G
Department of Medicine, University of Fribourg, Chemin du Musée 5, CH-1700 Fribourg, Switzerland.
Vilcu
Cristian
C
Neels
Jaap G
JG
Bandyopadhyay
Gautam K
GK
Luo
Jun-Li
JL
Naugler
Willscott
W
Grivennikov
Sergei
S
Wynshaw-Boris
Anthony
A
Scadeng
Miriam
M
Olefsky
Jerrold M
JM
Karin
Michael
M
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D004734:Energy Metabolism; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D010168:Palmitates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004041:Dietary Fats; D015850:Interleukin-6; D010168:Palmitates; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases