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

被引：115
作者：
Feng, Xudong [1 ]
Guan, Dongxian [1 ]
Auen, Thomas [1 ]
Choi, Jae Won [1 ]
Hernandez, Mario Andres Salazar [1 ]
Lee, Jaemin [1 ]
Chun, Hyonho [2 ]
Faruk, Farhana [1 ]
Kaplun, Esther [1 ]
Herbert, Zachary [3 ]
Copps, Kyle D. [1 ]
Ozcan, Umut [1 ]
机构：
[1] Harvard Med Sch, Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA
[2] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA
[3] Harvard Med Sch, Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02115 USA
来源：
NATURE MEDICINE | 2019年 / 25卷 / 04期
基金：
美国国家卫生研究院;
关键词：
UNFOLDED PROTEIN RESPONSE; RECEPTOR SUPERFAMILY; INSULIN SENSITIVITY; ENERGY-BALANCE; OBESITY; INFLAMMATION; RESISTANCE; STRESS; EXPRESSION; ANAKINRA;
D O I：
10.1038/s41591-019-0358-x
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：575 / +
页数：24
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