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Irisin Ameliorated Skeletal Muscle Atrophy by Inhibiting Fatty Acid Oxidation and Pyroptosis Induced by Palmitic Acid in Chronic Kidney Disease

INTRODUCTION: Protein-energy waste (PEW) is a common complication in patients with chronic kidney disease (CKD), among which skeletal muscle atrophy is one of the most important clinical features of PEW. Pyroptosis is a type of proinflammatory, programmed cell death associated with skeletal muscle d...

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Autores principales: Zhou, Ting, Wang, Shiyuan, Pan, Yajing, Dong, Xingtong, Wu, Leiyun, Meng, Jiali, Zhang, Jialing, Pang, Qi, Zhang, Aihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: S. Karger AG 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614467/
https://www.ncbi.nlm.nih.gov/pubmed/37717561
http://dx.doi.org/10.1159/000533926
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author Zhou, Ting
Wang, Shiyuan
Pan, Yajing
Dong, Xingtong
Wu, Leiyun
Meng, Jiali
Zhang, Jialing
Pang, Qi
Zhang, Aihua
author_facet Zhou, Ting
Wang, Shiyuan
Pan, Yajing
Dong, Xingtong
Wu, Leiyun
Meng, Jiali
Zhang, Jialing
Pang, Qi
Zhang, Aihua
author_sort Zhou, Ting
collection PubMed
description INTRODUCTION: Protein-energy waste (PEW) is a common complication in patients with chronic kidney disease (CKD), among which skeletal muscle atrophy is one of the most important clinical features of PEW. Pyroptosis is a type of proinflammatory, programmed cell death associated with skeletal muscle disease. Irisin, as a novel myokine, has attracted extensive attention for its protective role in the complications associated with CKD, but its role in muscle atrophy in CKD is unclear. METHODS: Palmitic acid (PA)-induced muscular atrophy was evaluated by a reduction in C2C12 myotube diameter. Muscle atrophy model was established in male C57BL/6J mice treated with 0.2% adenine for 4 weeks and then fed a 45% high-fat diet. Blood urea nitrogen and creatinine levels, body and muscle weight, and muscle histology were assessed. The expression of carnitine palmitoyltransferase 1A (CPT1A) and pyroptosis-related protein was analysed by Western blots or immunohistochemistry. The release of IL-1β was detected by enzyme-linked immunosorbent assay. RESULTS: In this study, we showed that PA-induced muscular atrophy manifested as a reduction in C2C12 myotube diameter. During this process, PA can also induce pyroptosis, as shown by the upregulation of NLRP3, cleaved caspase-1 and GSDMD-N expression and the increased IL-1β release and PI-positive cell rate. Inhibition of caspase-1 or NLRP3 attenuated PA-induced pyroptosis and myotube atrophy in C2C12 cells. Importantly, irisin treatment significantly ameliorated PA-induced skeletal muscle pyroptosis and atrophy. In terms of mechanism, PA upregulated CPT1A, a key enzyme of fatty acid oxidation (FAO), and irisin attenuated this effect, which was consistent with etomoxir (CPT1A inhibitor) treatment. Moreover, irisin improved skeletal muscle atrophy and pyroptosis in adenine-induced mice by regulating FAO. CONCLUSION: Our study firstly verifies that pyroptosis is a novel mechanism of skeletal muscle atrophy in CKD. Irisin ameliorates skeletal muscle atrophy by inhibiting FAO and pyroptosis in CKD, and irisin may be developed as a potential therapeutic agent for the treatment of muscle wasting in CKD patients.
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spelling pubmed-106144672023-10-31 Irisin Ameliorated Skeletal Muscle Atrophy by Inhibiting Fatty Acid Oxidation and Pyroptosis Induced by Palmitic Acid in Chronic Kidney Disease Zhou, Ting Wang, Shiyuan Pan, Yajing Dong, Xingtong Wu, Leiyun Meng, Jiali Zhang, Jialing Pang, Qi Zhang, Aihua Kidney Blood Press Res Research Article INTRODUCTION: Protein-energy waste (PEW) is a common complication in patients with chronic kidney disease (CKD), among which skeletal muscle atrophy is one of the most important clinical features of PEW. Pyroptosis is a type of proinflammatory, programmed cell death associated with skeletal muscle disease. Irisin, as a novel myokine, has attracted extensive attention for its protective role in the complications associated with CKD, but its role in muscle atrophy in CKD is unclear. METHODS: Palmitic acid (PA)-induced muscular atrophy was evaluated by a reduction in C2C12 myotube diameter. Muscle atrophy model was established in male C57BL/6J mice treated with 0.2% adenine for 4 weeks and then fed a 45% high-fat diet. Blood urea nitrogen and creatinine levels, body and muscle weight, and muscle histology were assessed. The expression of carnitine palmitoyltransferase 1A (CPT1A) and pyroptosis-related protein was analysed by Western blots or immunohistochemistry. The release of IL-1β was detected by enzyme-linked immunosorbent assay. RESULTS: In this study, we showed that PA-induced muscular atrophy manifested as a reduction in C2C12 myotube diameter. During this process, PA can also induce pyroptosis, as shown by the upregulation of NLRP3, cleaved caspase-1 and GSDMD-N expression and the increased IL-1β release and PI-positive cell rate. Inhibition of caspase-1 or NLRP3 attenuated PA-induced pyroptosis and myotube atrophy in C2C12 cells. Importantly, irisin treatment significantly ameliorated PA-induced skeletal muscle pyroptosis and atrophy. In terms of mechanism, PA upregulated CPT1A, a key enzyme of fatty acid oxidation (FAO), and irisin attenuated this effect, which was consistent with etomoxir (CPT1A inhibitor) treatment. Moreover, irisin improved skeletal muscle atrophy and pyroptosis in adenine-induced mice by regulating FAO. CONCLUSION: Our study firstly verifies that pyroptosis is a novel mechanism of skeletal muscle atrophy in CKD. Irisin ameliorates skeletal muscle atrophy by inhibiting FAO and pyroptosis in CKD, and irisin may be developed as a potential therapeutic agent for the treatment of muscle wasting in CKD patients. S. Karger AG 2023-09-15 /pmc/articles/PMC10614467/ /pubmed/37717561 http://dx.doi.org/10.1159/000533926 Text en © 2023 The Author(s). Published by S. Karger AG, Basel https://creativecommons.org/licenses/by-nc/4.0/This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.
spellingShingle Research Article
Zhou, Ting
Wang, Shiyuan
Pan, Yajing
Dong, Xingtong
Wu, Leiyun
Meng, Jiali
Zhang, Jialing
Pang, Qi
Zhang, Aihua
Irisin Ameliorated Skeletal Muscle Atrophy by Inhibiting Fatty Acid Oxidation and Pyroptosis Induced by Palmitic Acid in Chronic Kidney Disease
title Irisin Ameliorated Skeletal Muscle Atrophy by Inhibiting Fatty Acid Oxidation and Pyroptosis Induced by Palmitic Acid in Chronic Kidney Disease
title_full Irisin Ameliorated Skeletal Muscle Atrophy by Inhibiting Fatty Acid Oxidation and Pyroptosis Induced by Palmitic Acid in Chronic Kidney Disease
title_fullStr Irisin Ameliorated Skeletal Muscle Atrophy by Inhibiting Fatty Acid Oxidation and Pyroptosis Induced by Palmitic Acid in Chronic Kidney Disease
title_full_unstemmed Irisin Ameliorated Skeletal Muscle Atrophy by Inhibiting Fatty Acid Oxidation and Pyroptosis Induced by Palmitic Acid in Chronic Kidney Disease
title_short Irisin Ameliorated Skeletal Muscle Atrophy by Inhibiting Fatty Acid Oxidation and Pyroptosis Induced by Palmitic Acid in Chronic Kidney Disease
title_sort irisin ameliorated skeletal muscle atrophy by inhibiting fatty acid oxidation and pyroptosis induced by palmitic acid in chronic kidney disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614467/
https://www.ncbi.nlm.nih.gov/pubmed/37717561
http://dx.doi.org/10.1159/000533926
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