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An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice
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An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice
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Journal Article
An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice
2013
Overview
Alan Saltiel and his colleagues report that the approved drug amlexanox, currently used to treat asthma and canker sores, is a relatively specific inhibitor of the noncanonical IκB kinases IKK-ɛ and TANK-binding kinase 1 (TBK1) and that it improves metabolic disease in mouse genetic and dietary models of obesity. These results suggest this drug may be repurposed to treat obesity and insulin resistance.
Emerging evidence suggests that inflammation provides a link between obesity and insulin resistance. The noncanonical IκB kinases IKK-ɛ and TANK-binding kinase 1 (TBK1) are induced in liver and fat by NF-κB activation upon high-fat diet feeding and in turn initiate a program of counterinflammation that preserves energy storage. Here we report that amlexanox, an approved small-molecule therapeutic presently used in the clinic to treat aphthous ulcers and asthma, is an inhibitor of these kinases. Treatment of obese mice with amlexanox elevates energy expenditure through increased thermogenesis, producing weight loss, improved insulin sensitivity and decreased steatosis. Because of its record of safety in patients, amlexanox may be an interesting candidate for clinical evaluation in the treatment of obesity and related disorders.
Publisher
Nature Publishing Group US
Subject
/ Aminopyridines - pharmacology
/ Animals
/ Anti-Allergic Agents - pharmacology
/ Anti-Obesity Agents - pharmacology
/ Energy Metabolism - drug effects
/ Glucose Metabolism Disorders - drug therapy
/ I-kappa B Kinase - antagonists & inhibitors
/ I-kappa B Kinase - metabolism
/ Insulin Resistance - immunology
/ Intra-Abdominal Fat - drug effects
/ Intra-Abdominal Fat - metabolism
/ Male
/ Mice
/ Oxygen Consumption - drug effects
/ Protein Serine-Threonine Kinases - antagonists & inhibitors
