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

Feng, Xudong; Guan, Dongxian; Auen, Thomas; Choi, Jae Won; Salazar Hernández, Mario Andrés; Lee, Jaemin; Chun, Hyonho; Faruk, Farhana et al. · Nat Med · 2019

basic_science · Level V

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Abstract

Celastrol, a pentacyclic triterpene, is the most potent antiobesity agent that has been reported thus far<sup>1</sup>. 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.

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