IL1R1 is required for celastrol's leptin-sensitization and antiobesity effects.
basic_science · Level V
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- Record sourced from PubMed, PMID 30833749.
- Also identified by DOI 10.1038/s41591-019-0358-x and PMC identifier 7158951.
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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.
Medical subject headings
- Anti-Obesity Agents
- Leptin
- Obesity
- Receptors, Interleukin-1 Type I
- Triterpenes