title: The roles of c-Jun NH2-terminal kinases (JNKs) in obesity and insulin resistance.
abstract: Obesity is currently at epidemic levels worldwide and is associated with a wide range of diseases such as type 2 diabetes, cardiovascular disease, fatty liver disease and certain forms of cancer. Obesity-induced chronic inflammation is central to the disrupted metabolic homeostasis which underlies many of these conditions. While research over the past decade has identified many of the cells and signalling molecules that contribute to obesity-induced inflammation, perhaps the best characterised are the stress-activated c-Jun NH2 -terminal kinases (JNKs). JNKs are activated in obesity in numerous metabolically important cells and tissues such as adipose tissue, macrophages, liver, skeletal muscle and regions of the brain and pituitary. Elegant in vivo mouse studies using Cre-LoxP-mediated recombination of the JNK1 and JNK2 genes have revealed the remarkably diverse roles that JNKs play in the development of obesity-induced inflammation, impaired glucose homeostasis and hepatic steatosis. While JNK activation in classical metabolically active tissues such as skeletal muscle and adipose tissue only appears to play a minor role on the induction of the above-mentioned pathologies, recent studies have clearly established the important roles JNK signalling fulfils in macrophages, the liver and cells of the anterior pituitary. Collectively, these studies place JNKs as important mediators of obesity and obesity-associated disruptions to metabolic homeostasis.
authors.affiliation: Division of Diabetes and Metabolism, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Pal
authors.affiliation: Division of Diabetes and Metabolism, Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia.|Cellular & Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Febbraio
authors.affiliation: Cellular & Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Lancaster
mesh_terms: D000818:Animals; D006801:Humans; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D015290:Second Messenger Systems
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases