IL1R1 is required for celastrol's leptin-sensitization and antiobesity effects

Celastrol, a pentacyclic triterpene, is the most potent antiobesity agent that has been reported thus far.sup.1. The mechanism of celastrol's leptin-sensitizing and antiobesity effects has not yet been elucidated. In this study, we identified interleukin-1 receptor 1 (IL1R1) as a mediator of celastrol's action by using temporally resolved analysis of the hypothalamic transcriptome in celastrol-treated DIO, lean, and db/db mice. We demonstrate that IL1R1-deficient mice are completely resistant to the effects of celastrol in leptin sensitization and treatment of obesity, diabetes, and nonalcoholic steatohepatitis. Thus, we conclude that IL1R1 is a gatekeeper for celastrol's metabolic actions. IL1R1 is a gatekeeper for celastrol's metabolic actions.
Author(s): Xudong Feng [sup.1] , Dongxian Guan [sup.1] , Thomas Auen [sup.1] , Jae Won Choi [sup.1] , Mario Andrés Salazar Hernández [sup.1] , Jaemin Lee [sup.1] , Hyonho Chun [...]