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Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2

Non-alcoholic fatty liver disease (NAFLD) is a global clinical problem. The MD2-TLR4 pathway exacerbates NAFLD progression by promoting inflammation. Long-term exercise is considered to improve NAFLD but the underlying mechanism is still unclear. In this study, we examined the protective effect and...

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Autores principales: Zhu, Weiwei, Sahar, Namood E, Javaid, Hafiz Muhammad Ahmad, Pak, Eun Seon, Liang, Guang, Wang, Yi, Ha, Hunjoo, Huh, Joo Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699279/
https://www.ncbi.nlm.nih.gov/pubmed/34943814
http://dx.doi.org/10.3390/cells10123306
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author Zhu, Weiwei
Sahar, Namood E
Javaid, Hafiz Muhammad Ahmad
Pak, Eun Seon
Liang, Guang
Wang, Yi
Ha, Hunjoo
Huh, Joo Young
author_facet Zhu, Weiwei
Sahar, Namood E
Javaid, Hafiz Muhammad Ahmad
Pak, Eun Seon
Liang, Guang
Wang, Yi
Ha, Hunjoo
Huh, Joo Young
author_sort Zhu, Weiwei
collection PubMed
description Non-alcoholic fatty liver disease (NAFLD) is a global clinical problem. The MD2-TLR4 pathway exacerbates NAFLD progression by promoting inflammation. Long-term exercise is considered to improve NAFLD but the underlying mechanism is still unclear. In this study, we examined the protective effect and molecular mechanism of exercise on high-fat diet (HFD)-induced liver injury. In an HFD-induced NAFLD mouse model, exercise training significantly decreased hepatic steatosis and fibrosis. Interestingly, exercise training blocked the binding of MD2-TLR4 and decreased the downstream inflammatory response. Irisin is a myokine that is highly expressed in response to exercise and exerts anti-inflammatory effects. We found that circulating irisin levels and muscle irisin expression were significantly increased in exercised mice, suggesting that irisin could mediate the effect of exercise on NAFLD. In vitro studies showed that irisin improved lipid metabolism, fibrosis, and inflammation in palmitic acid (PA)-stimulated AML12 cells. Moreover, binding assay results showed that irisin disturbed MD2-TLR4 complex formation by directly binding with MD2 but not TLR4, and interfered with the recognition of stimuli such as PA and lipopolysaccharide with MD2. Our study provides novel evidence that exercise-induced irisin inhibits inflammation via competitive binding with MD2 to improve NAFLD. Thus, irisin could be considered a potential therapy for NAFLD.
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spelling pubmed-86992792021-12-24 Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2 Zhu, Weiwei Sahar, Namood E Javaid, Hafiz Muhammad Ahmad Pak, Eun Seon Liang, Guang Wang, Yi Ha, Hunjoo Huh, Joo Young Cells Article Non-alcoholic fatty liver disease (NAFLD) is a global clinical problem. The MD2-TLR4 pathway exacerbates NAFLD progression by promoting inflammation. Long-term exercise is considered to improve NAFLD but the underlying mechanism is still unclear. In this study, we examined the protective effect and molecular mechanism of exercise on high-fat diet (HFD)-induced liver injury. In an HFD-induced NAFLD mouse model, exercise training significantly decreased hepatic steatosis and fibrosis. Interestingly, exercise training blocked the binding of MD2-TLR4 and decreased the downstream inflammatory response. Irisin is a myokine that is highly expressed in response to exercise and exerts anti-inflammatory effects. We found that circulating irisin levels and muscle irisin expression were significantly increased in exercised mice, suggesting that irisin could mediate the effect of exercise on NAFLD. In vitro studies showed that irisin improved lipid metabolism, fibrosis, and inflammation in palmitic acid (PA)-stimulated AML12 cells. Moreover, binding assay results showed that irisin disturbed MD2-TLR4 complex formation by directly binding with MD2 but not TLR4, and interfered with the recognition of stimuli such as PA and lipopolysaccharide with MD2. Our study provides novel evidence that exercise-induced irisin inhibits inflammation via competitive binding with MD2 to improve NAFLD. Thus, irisin could be considered a potential therapy for NAFLD. MDPI 2021-11-25 /pmc/articles/PMC8699279/ /pubmed/34943814 http://dx.doi.org/10.3390/cells10123306 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhu, Weiwei
Sahar, Namood E
Javaid, Hafiz Muhammad Ahmad
Pak, Eun Seon
Liang, Guang
Wang, Yi
Ha, Hunjoo
Huh, Joo Young
Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2
title Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2
title_full Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2
title_fullStr Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2
title_full_unstemmed Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2
title_short Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2
title_sort exercise-induced irisin decreases inflammation and improves nafld by competitive binding with md2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699279/
https://www.ncbi.nlm.nih.gov/pubmed/34943814
http://dx.doi.org/10.3390/cells10123306
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