An inhibitor of the protein kinases TBK1 and IKK-epsilon improves obesity-related metabolic dysfunctions in mice

作者：Reilly Shannon M; Chiang Shian Huey; Decker Stuart J; Chang Louise; Uhm Maeran; Larsen Martha J; Rubin John R; Mowers Jonathan; White Nicole M; Hochberg Irit; Downes Michael; Yu Ruth T; Liddle Christopher; Evans Ronald M; Oh Dayoung; Li Pingping; Olefsky Jerrold M; Saltiel Alan R^*

来源：Nature Medicine, 2013, 19(3): 313-321.

DOI：10.1038/nm.3082

Emerging evidence suggests that inflammation provides a link between obesity and insulin resistance. The noncanonical I kappa B kinases IKK-epsilon and TANK-binding kinase 1 (TBK1) are induced in liver and fat by NF-kappa B 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.

• 出版日期2013-3