title: An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice.
abstract: 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.
authors: Life Sciences Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
authors: Shannon M
authors: SM
authors: Reilly
authors: Shian-Huey
authors: SH
authors: Chiang
authors: Stuart J
authors: SJ
authors: Decker
authors: Louise
authors: L
authors: Chang
authors: Maeran
authors: M
authors: Uhm
authors: Martha J
authors: MJ
authors: Larsen
authors: John R
authors: JR
authors: Rubin
authors: Jonathan
authors: J
authors: Mowers
authors: Nicole M
authors: NM
authors: White
authors: Irit
authors: I
authors: Hochberg
authors: Michael
authors: M
authors: Downes
authors: Ruth T
authors: RT
authors: Yu
authors: Christopher
authors: C
authors: Liddle
authors: Ronald M
authors: RM
authors: Evans
authors: Dayoung
authors: D
authors: Oh
authors: Pingping
authors: P
authors: Li
authors: Jerrold M
authors: JM
authors: Olefsky
authors: Alan R
authors: AR
authors: Saltiel
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D002460:Cell Line; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000187:drug effects*; D004789:Enzyme Activation; D005234:Fatty Liver / Q000188:drug therapy; D044882:Glucose Metabolism Disorders / Q000188:drug therapy; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007333:Insulin Resistance / Q000276:immunology; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000631:Aminopyridines; D018926:Anti-Allergic Agents; D019440:Anti-Obesity Agents; D016328:NF-kappa B; C045742:amlexanox; C498588:Tbk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase
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