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

Xudong Feng; Dongxian Guan; Thomas Auen; Jae Won Choi; Mario Andrés Salazar Hernández; Jaemin Lee; Hyonho Chun; Farhana Faruk; Esther Kaplun; Zachary Herbert; Kyle D. Copps; Umut Ozcan

doi:10.1038/s41591-019-0358-x

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

Xudong Feng
, Dongxian Guan
, Thomas Auen
, Jae Won Choi
, Mario Andrés Salazar Hernández
, Jaemin Lee
, Hyonho Chun
, Farhana Faruk
, Esther Kaplun
, Zachary Herbert
, Kyle D. Copps
, Umut Ozcan

Department of New Biology

Research output: Contribution to journal › Article › peer-review

121 Scopus citations

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.

Original language	English
Pages (from-to)	575-582
Number of pages	8
Journal	Nature Medicine
Volume	25
Issue number	4
DOIs	https://doi.org/10.1038/s41591-019-0358-x
State	Published - 1 Apr 2019

Bibliographical note

Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/s41591-019-0358-x

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title = "IL1R1 is required for celastrol{\textquoteright}s leptin-sensitization and antiobesity effects",

abstract = "Celastrol, a pentacyclic triterpene, is the most potent antiobesity agent that has been reported thus far1. The mechanism of celastrol{\textquoteright}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{\textquoteright}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{\textquoteright}s metabolic actions.",

author = "Xudong Feng and Dongxian Guan and Thomas Auen and Choi, \{Jae Won\} and \{Salazar Hern{\'a}ndez\}, \{Mario Andr{\'e}s\} and Jaemin Lee and Hyonho Chun and Farhana Faruk and Esther Kaplun and Zachary Herbert and Copps, \{Kyle D.\} and Umut Ozcan",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2019",

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doi = "10.1038/s41591-019-0358-x",

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TY - JOUR

T1 - IL1R1 is required for celastrol’s leptin-sensitization and antiobesity effects

AU - Feng, Xudong

AU - Guan, Dongxian

AU - Auen, Thomas

AU - Choi, Jae Won

AU - Salazar Hernández, Mario Andrés

AU - Lee, Jaemin

AU - Chun, Hyonho

AU - Faruk, Farhana

AU - Kaplun, Esther

AU - Herbert, Zachary

AU - Copps, Kyle D.

AU - Ozcan, Umut

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85062600388

U2 - 10.1038/s41591-019-0358-x

DO - 10.1038/s41591-019-0358-x

M3 - Article

C2 - 30833749

AN - SCOPUS:85062600388

SN - 1078-8956

VL - 25

SP - 575

EP - 582

JO - Nature Medicine

JF - Nature Medicine

IS - 4

ER -

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

Abstract

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UN SDGs

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