A central role for JNK in obesity and insulin resistance
- PMID: 12447443
- DOI: 10.1038/nature01137
A central role for JNK in obesity and insulin resistance
Erratum in
-
Author Correction: A central role for JNK in obesity and insulin resistance.Nature. 2023 Jul;619(7968):E25. doi: 10.1038/s41586-023-06285-0. Nature. 2023. PMID: 37328696 No abstract available.
Abstract
Obesity is closely associated with insulin resistance and establishes the leading risk factor for type 2 diabetes mellitus, yet the molecular mechanisms of this association are poorly understood. The c-Jun amino-terminal kinases (JNKs) can interfere with insulin action in cultured cells and are activated by inflammatory cytokines and free fatty acids, molecules that have been implicated in the development of type 2 diabetes. Here we show that JNK activity is abnormally elevated in obesity. Furthermore, an absence of JNK1 results in decreased adiposity, significantly improved insulin sensitivity and enhanced insulin receptor signalling capacity in two different models of mouse obesity. Thus, JNK is a crucial mediator of obesity and insulin resistance and a potential target for therapeutics.
Similar articles
-
Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes.Science. 2004 Oct 15;306(5695):457-61. doi: 10.1126/science.1103160. Science. 2004. PMID: 15486293
-
c-Jun N-terminal kinase (JNK) mediates feedback inhibition of the insulin signaling cascade.J Biol Chem. 2003 Jan 31;278(5):2896-902. doi: 10.1074/jbc.M208359200. Epub 2002 Nov 1. J Biol Chem. 2003. PMID: 12417588
-
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity.Nature. 2004 Sep 9;431(7005):200-5. doi: 10.1038/nature02866. Epub 2004 Aug 11. Nature. 2004. PMID: 15306821
-
Inflammation and endoplasmic reticulum stress in obesity and diabetes.Int J Obes (Lond). 2008 Dec;32 Suppl 7(Suppl 7):S52-4. doi: 10.1038/ijo.2008.238. Int J Obes (Lond). 2008. PMID: 19136991 Free PMC article. Review.
-
[Obesity, diabetes and insulin resistance. Alterations of insulin signalling].J Soc Biol. 2006;200(1):93-7. doi: 10.1051/jbio:2006012. J Soc Biol. 2006. PMID: 17144167 Review. French.
Cited by
-
Chronic tissue inflammation and metabolic disease.Genes Dev. 2021 Mar 1;35(5-6):307-328. doi: 10.1101/gad.346312.120. Genes Dev. 2021. PMID: 33649162 Free PMC article. Review.
-
The Effects of Long-Term, Low-Level Exposure to Monocyclic Aromatic Hydrocarbons on Worker's Insulin Resistance.Saf Health Work. 2011 Dec;2(4):365-74. doi: 10.5491/SHAW.2011.2.4.365. Epub 2011 Oct 6. Saf Health Work. 2011. PMID: 22953221 Free PMC article.
-
Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis.Science. 2013 Jan 11;339(6116):172-7. doi: 10.1126/science.1230721. Science. 2013. PMID: 23307735 Free PMC article. Review.
-
A novel plasminogen activator inhibitor-1 inhibitor, TM5441, protects against high-fat diet-induced obesity and adipocyte injury in mice.Br J Pharmacol. 2016 Sep;173(17):2622-32. doi: 10.1111/bph.13541. Epub 2016 Jul 28. Br J Pharmacol. 2016. PMID: 27339909 Free PMC article.
-
Toll-like receptor 4 knockout mice are protected against endoplasmic reticulum stress induced by a high-fat diet.PLoS One. 2013 May 31;8(5):e65061. doi: 10.1371/journal.pone.0065061. Print 2013. PLoS One. 2013. PMID: 23741455 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous