Abstract
Celastrol, a pentacyclic triterpene is the most potent anti-obesity agent that has been reported to date1. The mechanism of celastrol’s leptin sensitizing and anti-obesity effects has not yet been elucidated. In this study, we identified interleukin 1 receptor 1 (IL1R1) as a mediator of celastrol 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 celastrol’s leptin sensitization, anti-obesity, anti-diabetic and anti-NASH effects. Thus, we conclude that IL1R1 is a gate-keeper for celastrol’s metabolic actions.
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