The drug amlexanox, which is currently used to treat asthma in Japan and open sores in the mouth in the US, may be beneficial in treating obesity and type 2 diabetes in mice, according to study published this week in Nature Medicine.
Obesity is often associated with a state of low-grade inflammation, which is believed to contribute to insulin resistance and the development of type 2 diabetes. Using a large-scale in vitro chemical screen Alan Saltiel and colleagues now identify small molecule inhibitors of IKK-epsilon and a highly related kinase called TBK1. One of these inhibitors includes amlexanox, which they show is a relatively selective inhibitor of these two kinases. They also report that amlexanox produced reversible weight loss in a dietary and a genetic mouse model of obesity through an increase in energy expenditure. Further, the drug improved the insulin sensitivity and reversed fatty liver disease in these mice, even before a change in weight. These effects were associated with a reduction in adipose tissue inflammation and seemed to depend on the expression of IKK-epsilon and TBK1.
Amlexanox has a long history of use in people and with a good safety record. Although future clinical studies are needed, repurposing of the drug to treat obesity and its metabolic complications may be a valid option in the clinic.