The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia

Abstract Cytokines such as IL-6, TNF-α and IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 nephrectomy in mice. We studied energy homeostasis in Il1β −/− /CKD, Il6 −/− /CKD and Tnfα −/− /CKD mic...

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Autores principales:	Wai W. Cheung, Ronghao Zheng, Sheng Hao, Zhen Wang, Alex Gonzalez, Ping Zhou, Hal M. Hoffman, Robert H. Mak
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e4b1d33e01524a95bb59afcecfed6c92
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spelling	oai:doaj.org-article:e4b1d33e01524a95bb59afcecfed6c922021-12-02T16:17:34ZThe role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia10.1038/s41598-021-94565-y2045-2322https://doaj.org/article/e4b1d33e01524a95bb59afcecfed6c922021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94565-yhttps://doaj.org/toc/2045-2322Abstract Cytokines such as IL-6, TNF-α and IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 nephrectomy in mice. We studied energy homeostasis in Il1β −/− /CKD, Il6 −/− /CKD and Tnfα −/− /CKD mice and compared with wild type (WT)/CKD controls. Parameters of cachexia phenotype were completely normalized in Il1β −/− /CKD mice but were only partially rescued in Il6 −/− /CKD and Tnfα −/− /CKD mice. We tested the effects of anakinra, an IL-1 receptor antagonist, on CKD-associated cachexia. WT/CKD mice were treated with anakinra (2.5 mg/kg/day, IP) or saline for 6 weeks and compared with WT/Sham controls. Anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function, and also attenuated molecular perturbations of energy homeostasis in adipose tissue and muscle in WT/CKD mice. Anakinra decreased serum and muscle expression of IL-6, TNF-α and IL-1β in WT/CKD mice. Anakinra attenuated browning of white adipose tissue in WT/CKD mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in WT/CKD mice. This was accompanied by correcting the increased muscle wasting signaling pathways while promoting the decreased myogenesis process in gastrocnemius of WT/CKD mice. We performed qPCR analysis for the top 20 differentially expressed muscle genes previously identified via RNAseq analysis in WT/CKD mice versus controls. Importantly, 17 differentially expressed muscle genes were attenuated in anakinra treated WT/CKD mice. In conclusion, IL-1 receptor antagonism may represent a novel targeted treatment for adipose tissue browning and muscle wasting in CKD.Wai W. CheungRonghao ZhengSheng HaoZhen WangAlex GonzalezPing ZhouHal M. HoffmanRobert H. MakNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wai W. Cheung Ronghao Zheng Sheng Hao Zhen Wang Alex Gonzalez Ping Zhou Hal M. Hoffman Robert H. Mak The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia
description	Abstract Cytokines such as IL-6, TNF-α and IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 nephrectomy in mice. We studied energy homeostasis in Il1β −/− /CKD, Il6 −/− /CKD and Tnfα −/− /CKD mice and compared with wild type (WT)/CKD controls. Parameters of cachexia phenotype were completely normalized in Il1β −/− /CKD mice but were only partially rescued in Il6 −/− /CKD and Tnfα −/− /CKD mice. We tested the effects of anakinra, an IL-1 receptor antagonist, on CKD-associated cachexia. WT/CKD mice were treated with anakinra (2.5 mg/kg/day, IP) or saline for 6 weeks and compared with WT/Sham controls. Anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function, and also attenuated molecular perturbations of energy homeostasis in adipose tissue and muscle in WT/CKD mice. Anakinra decreased serum and muscle expression of IL-6, TNF-α and IL-1β in WT/CKD mice. Anakinra attenuated browning of white adipose tissue in WT/CKD mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in WT/CKD mice. This was accompanied by correcting the increased muscle wasting signaling pathways while promoting the decreased myogenesis process in gastrocnemius of WT/CKD mice. We performed qPCR analysis for the top 20 differentially expressed muscle genes previously identified via RNAseq analysis in WT/CKD mice versus controls. Importantly, 17 differentially expressed muscle genes were attenuated in anakinra treated WT/CKD mice. In conclusion, IL-1 receptor antagonism may represent a novel targeted treatment for adipose tissue browning and muscle wasting in CKD.
format	article
author	Wai W. Cheung Ronghao Zheng Sheng Hao Zhen Wang Alex Gonzalez Ping Zhou Hal M. Hoffman Robert H. Mak
author_facet	Wai W. Cheung Ronghao Zheng Sheng Hao Zhen Wang Alex Gonzalez Ping Zhou Hal M. Hoffman Robert H. Mak
author_sort	Wai W. Cheung
title	The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia
title_short	The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia
title_full	The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia
title_fullStr	The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia
title_full_unstemmed	The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia
title_sort	role of il-1 in adipose browning and muscle wasting in ckd-associated cachexia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e4b1d33e01524a95bb59afcecfed6c92
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The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia

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