Format

Send to

Choose Destination
Nat Med. 2019 Apr;25(4):575-582. doi: 10.1038/s41591-019-0358-x. Epub 2019 Mar 4.

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

Author information

1
Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
2
Department of Mathematics and Statistics, Boston University, Boston, MA, USA.
3
Molecular Biology Core Facilities, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
4
Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. umut.ozcan@childrens.harvard.edu.

Abstract

Celastrol, a pentacyclic triterpene, is the most potent antiobesity agent that has been reported thus far1. 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.

PMID:
30833749
DOI:
10.1038/s41591-019-0358-x
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center