title: JNK expression by macrophages promotes obesity-induced insulin resistance and inflammation.
abstract: The cJun NH(2)-terminal kinase (JNK) signaling pathway contributes to inflammation and plays a key role in the metabolic response to obesity, including insulin resistance. Macrophages are implicated in this process. To test the role of JNK, we established mice with selective JNK deficiency in macrophages. We report that feeding a high-fat diet to control and JNK-deficient mice caused similar obesity, but only mice with JNK-deficient macrophages remained insulin-sensitive. The protection of mice with macrophage-specific JNK deficiency against insulin resistance was associated with reduced tissue infiltration by macrophages. Immunophenotyping demonstrated that JNK was required for pro-inflammatory macrophage polarization. These studies demonstrate that JNK in macrophages is required for the establishment of obesity-induced insulin resistance and inflammation.
authors.affiliation: Howard Hughes Medical Institute, Worcester, MA 01605, USA.
authors.forename: Myoung Sook
authors.initials: MS
authors.lastname: Han
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Jung
authors.forename: Caroline
authors.initials: C
authors.lastname: Morel
authors.forename: Saquib A
authors.initials: SA
authors.lastname: Lakhani
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000473:pathology; D000818:Animals; D059305:Diet, High-Fat; D015309:Glucose Clamp Technique; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000473:pathology; D020935:MAP Kinase Signaling System; D008262:Macrophage Activation; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology* / Q000502:physiology; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000276:immunology / Q000503:physiopathology*
chemical_list: D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8