Journal
NATURE MEDICINE
Volume 25, Issue 4, Pages 575-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41591-019-0358-x
Keywords
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Funding
- Department of Medicine
- Smith President's Innovation Award from Boston Children's Hospital
- National Institutes of Health [R01DK098496, R56DK098496]
- Fidelity Biosciences Research Initiative
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Celastrol, a pentacyclic triterpene, is the most potent antiobesity agent that has been reported thus far(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.
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