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

Celastrol, a pentacyclic triterpene is the most potent anti-obesity agent that has been reported to date(1). The mechanism of celastrol’s leptin sensitizing and anti-obesity effects has not yet been elucidated. In this study, we identified interleukin 1 receptor 1 (IL1R1) as a mediator of celastrol...

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Autores principales: Feng, Xudong, Guan, Dongxian, Auen, Thomas, Choi, Jae Won, Salazar Hernández, Mario Andrés, Lee, Jaemin, Chun, Hyonho, Faruk, Farhana, Kaplun, Esther, Herbert, Zachary, Copps, Kyle D., Ozcan, Umut
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158951/
https://www.ncbi.nlm.nih.gov/pubmed/30833749
http://dx.doi.org/10.1038/s41591-019-0358-x
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author Feng, Xudong
Guan, Dongxian
Auen, Thomas
Choi, Jae Won
Salazar Hernández, Mario Andrés
Lee, Jaemin
Chun, Hyonho
Faruk, Farhana
Kaplun, Esther
Herbert, Zachary
Copps, Kyle D.
Ozcan, Umut
author_facet Feng, Xudong
Guan, Dongxian
Auen, Thomas
Choi, Jae Won
Salazar Hernández, Mario Andrés
Lee, Jaemin
Chun, Hyonho
Faruk, Farhana
Kaplun, Esther
Herbert, Zachary
Copps, Kyle D.
Ozcan, Umut
author_sort Feng, Xudong
collection PubMed
description Celastrol, a pentacyclic triterpene is the most potent anti-obesity agent that has been reported to date(1). The mechanism of celastrol’s leptin sensitizing and anti-obesity effects has not yet been elucidated. In this study, we identified interleukin 1 receptor 1 (IL1R1) as a mediator of celastrol 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 celastrol’s leptin sensitization, anti-obesity, anti-diabetic and anti-NASH effects. Thus, we conclude that IL1R1 is a gate-keeper for celastrol’s metabolic actions.
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spelling pubmed-71589512020-04-15 IL1R1 is required for celastrol’s leptin sensitization and anti-obesity effects Feng, Xudong Guan, Dongxian Auen, Thomas Choi, Jae Won Salazar Hernández, Mario Andrés Lee, Jaemin Chun, Hyonho Faruk, Farhana Kaplun, Esther Herbert, Zachary Copps, Kyle D. Ozcan, Umut Nat Med Article Celastrol, a pentacyclic triterpene is the most potent anti-obesity agent that has been reported to date(1). The mechanism of celastrol’s leptin sensitizing and anti-obesity effects has not yet been elucidated. In this study, we identified interleukin 1 receptor 1 (IL1R1) as a mediator of celastrol 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 celastrol’s leptin sensitization, anti-obesity, anti-diabetic and anti-NASH effects. Thus, we conclude that IL1R1 is a gate-keeper for celastrol’s metabolic actions. 2019-03-04 2019-04 /pmc/articles/PMC7158951/ /pubmed/30833749 http://dx.doi.org/10.1038/s41591-019-0358-x Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Feng, Xudong
Guan, Dongxian
Auen, Thomas
Choi, Jae Won
Salazar Hernández, Mario Andrés
Lee, Jaemin
Chun, Hyonho
Faruk, Farhana
Kaplun, Esther
Herbert, Zachary
Copps, Kyle D.
Ozcan, Umut
IL1R1 is required for celastrol’s leptin sensitization and anti-obesity effects
title IL1R1 is required for celastrol’s leptin sensitization and anti-obesity effects
title_full IL1R1 is required for celastrol’s leptin sensitization and anti-obesity effects
title_fullStr IL1R1 is required for celastrol’s leptin sensitization and anti-obesity effects
title_full_unstemmed IL1R1 is required for celastrol’s leptin sensitization and anti-obesity effects
title_short IL1R1 is required for celastrol’s leptin sensitization and anti-obesity effects
title_sort il1r1 is required for celastrol’s leptin sensitization and anti-obesity effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158951/
https://www.ncbi.nlm.nih.gov/pubmed/30833749
http://dx.doi.org/10.1038/s41591-019-0358-x
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