{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T22:43:47Z","timestamp":1792363427108,"version":"4.4.0"},"reference-count":60,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1C1B6003470"],"award-info":[{"award-number":["2018R1C1B6003470"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1H1A1012282"],"award-info":[{"award-number":["2021R1H1A1012282"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells10123306","type":"journal-article","created":{"date-parts":[[2021,11,28]],"date-time":"2021-11-28T22:19:16Z","timestamp":1638137956000},"page":"3306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["Exercise-Induced Irisin Decreases Inflammation and Improves NAFLD by Competitive Binding with MD2"],"prefix":"10.3390","volume":"10","author":[{"given":"Weiwei","family":"Zhu","sequence":"first","affiliation":[{"name":"College of Pharmacy, Chonnam National University, Gwangju 61186, Korea"},{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namood E","family":"Sahar","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1373-4524","authenticated-orcid":false,"given":"Hafiz Muhammad Ahmad","family":"Javaid","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Seon","family":"Pak","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Liang","sequence":"additional","affiliation":[{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5601-1265","authenticated-orcid":false,"given":"Hunjoo","family":"Ha","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6682-4764","authenticated-orcid":false,"given":"Joo Young","family":"Huh","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8263","DOI":"10.3748\/wjg.v23.i47.8263","article-title":"Clinical epidemiology and disease burden of nonalcoholic fatty liver disease","volume":"23","author":"Perumpail","year":"2017","journal-title":"World J. 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