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

被引：124

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

页码：575 / +

页数：24

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