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Rapamycin suppresses inflammation and increases the interaction between p65 and IκBα in rapamycin-induced fatty livers

Rapamycin treatment significantly increases lifespan and ameliorates several aging-related diseases in mice, making it a potential anti-aging drug. However, there are several obvious side effects of rapamycin, which may limit the broad applications of this drug. Lipid metabolism disorders such as fa...

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Autores principales: Ge, Chenliang, Ma, Changguo, Cui, Jiesheng, Dong, Xingbo, Sun, Luyang, Li, Yanjiao, Yu, An
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9983852/
https://www.ncbi.nlm.nih.gov/pubmed/36867603
http://dx.doi.org/10.1371/journal.pone.0281888
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author Ge, Chenliang
Ma, Changguo
Cui, Jiesheng
Dong, Xingbo
Sun, Luyang
Li, Yanjiao
Yu, An
author_facet Ge, Chenliang
Ma, Changguo
Cui, Jiesheng
Dong, Xingbo
Sun, Luyang
Li, Yanjiao
Yu, An
author_sort Ge, Chenliang
collection PubMed
description Rapamycin treatment significantly increases lifespan and ameliorates several aging-related diseases in mice, making it a potential anti-aging drug. However, there are several obvious side effects of rapamycin, which may limit the broad applications of this drug. Lipid metabolism disorders such as fatty liver and hyperlipidemia are some of those unwanted side effects. Fatty liver is characterized as ectopic lipid accumulation in livers, which is usually accompanied by increased inflammation levels. Rapamycin is also a well-known anti-inflammation chemical. How rapamycin affects the inflammation level in rapamycin-induced fatty liver remains poorly understood. Here, we show that eight-day rapamycin treatment induced fatty liver and increased liver free fatty acid levels in mice, while the expression levels of inflammatory markers are even lower than those in the control mice. Mechanistically, the upstream of the pro-inflammatory pathway was activated in rapamycin-induced fatty livers, however, there is no increased NFκB nuclear translocation probably because the interaction between p65 and IκBα was enhanced by rapamycin treatment. The lipolysis pathway in the liver is also suppressed by rapamycin. Liver cirrhosis is an adverse consequence of fatty liver, while prolonged rapamycin treatment did not increase liver cirrhosis markers. Our results indicate that although fatty livers are induced by rapamycin, the fatty livers are not accompanied by increased inflammation levels, implying that rapamycin-induced fatty livers might not be as harmful as other types of fatty livers, such as high-fat diet and alcohol-induced fatty livers.
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spelling pubmed-99838522023-03-04 Rapamycin suppresses inflammation and increases the interaction between p65 and IκBα in rapamycin-induced fatty livers Ge, Chenliang Ma, Changguo Cui, Jiesheng Dong, Xingbo Sun, Luyang Li, Yanjiao Yu, An PLoS One Research Article Rapamycin treatment significantly increases lifespan and ameliorates several aging-related diseases in mice, making it a potential anti-aging drug. However, there are several obvious side effects of rapamycin, which may limit the broad applications of this drug. Lipid metabolism disorders such as fatty liver and hyperlipidemia are some of those unwanted side effects. Fatty liver is characterized as ectopic lipid accumulation in livers, which is usually accompanied by increased inflammation levels. Rapamycin is also a well-known anti-inflammation chemical. How rapamycin affects the inflammation level in rapamycin-induced fatty liver remains poorly understood. Here, we show that eight-day rapamycin treatment induced fatty liver and increased liver free fatty acid levels in mice, while the expression levels of inflammatory markers are even lower than those in the control mice. Mechanistically, the upstream of the pro-inflammatory pathway was activated in rapamycin-induced fatty livers, however, there is no increased NFκB nuclear translocation probably because the interaction between p65 and IκBα was enhanced by rapamycin treatment. The lipolysis pathway in the liver is also suppressed by rapamycin. Liver cirrhosis is an adverse consequence of fatty liver, while prolonged rapamycin treatment did not increase liver cirrhosis markers. Our results indicate that although fatty livers are induced by rapamycin, the fatty livers are not accompanied by increased inflammation levels, implying that rapamycin-induced fatty livers might not be as harmful as other types of fatty livers, such as high-fat diet and alcohol-induced fatty livers. Public Library of Science 2023-03-03 /pmc/articles/PMC9983852/ /pubmed/36867603 http://dx.doi.org/10.1371/journal.pone.0281888 Text en © 2023 Ge et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ge, Chenliang
Ma, Changguo
Cui, Jiesheng
Dong, Xingbo
Sun, Luyang
Li, Yanjiao
Yu, An
Rapamycin suppresses inflammation and increases the interaction between p65 and IκBα in rapamycin-induced fatty livers
title Rapamycin suppresses inflammation and increases the interaction between p65 and IκBα in rapamycin-induced fatty livers
title_full Rapamycin suppresses inflammation and increases the interaction between p65 and IκBα in rapamycin-induced fatty livers
title_fullStr Rapamycin suppresses inflammation and increases the interaction between p65 and IκBα in rapamycin-induced fatty livers
title_full_unstemmed Rapamycin suppresses inflammation and increases the interaction between p65 and IκBα in rapamycin-induced fatty livers
title_short Rapamycin suppresses inflammation and increases the interaction between p65 and IκBα in rapamycin-induced fatty livers
title_sort rapamycin suppresses inflammation and increases the interaction between p65 and iκbα in rapamycin-induced fatty livers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9983852/
https://www.ncbi.nlm.nih.gov/pubmed/36867603
http://dx.doi.org/10.1371/journal.pone.0281888
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