2043-P: The Biphasic Antiobesogenic Effects of Amlexanox

Abstract

Obesity is associated with a chronic, low-grade inflammation that plays a key role in the development of insulin and catecholamine resistance. Amlexanox (Amx), an inhibitor of the inflammatory kinases TBK1 and IKKε, has been shown to improve insulin sensitivity and promote weight loss in mice. Here, we elucidate the anti-obesogenic effects of Amx. Diet induced obese mice were treated with Amx or vehicle control via oral gavage. Amx treatment caused a transient drop in food intake that normalized after 7 days. After, Amx treated mice continued to lose weight suggesting food-independent drivers of weight loss. Furthermore, Amx treated animals exhibited increased energy expenditure compared to pair-fed vehicle control mice. Increased energy expenditure in Amx treated mice is likely due to beiging of white adipose tissue as UCP1 KO mice exhibit a defect in weight loss after food intake normalizes. These data suggest Amx transiently down-regulates food consumption through an unknown mechanism while continuously promoting energy expenditure through beige fat. We conclude that Amx promotes weight loss through a biphasic mechanism involving an early transient decrease in food intake and long term increased thermogenesis via beiging of white fat. Further research will focus on the molecular mechanism controlling beiging and investigate possible central effects of Amx on food consumption. Disclosure A.V. Gomez: None. S. Reilly: None. M. Abu Odeh: None. E. Walk: None. A. Saltiel: None. Funding National Institutes of Health