Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction
Background Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects...
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Korean Endocrine Society
2024-12-01
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| Series: | Endocrinology and Metabolism |
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| Online Access: | http://www.e-enm.org/upload/pdf/enm-2024-1984.pdf |
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| author | Thuy Linh Lai So Young Park Giang Nguyen Phuc Thi Minh Pham Seon Mee Kang Jeana Hong Jae-Ho Lee Seung-Soon Im Dae-Hee Choi Eun-Hee Cho |
| author_facet | Thuy Linh Lai So Young Park Giang Nguyen Phuc Thi Minh Pham Seon Mee Kang Jeana Hong Jae-Ho Lee Seung-Soon Im Dae-Hee Choi Eun-Hee Cho |
| author_sort | Thuy Linh Lai |
| collection | DOAJ |
| description | Background Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction. Methods In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days. Results In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery. Conclusion Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis. |
| format | Article |
| id | doaj-art-65b4d63af43b44f0b59ab7a784899f2f |
| institution | Kabale University |
| issn | 2093-596X 2093-5978 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Korean Endocrine Society |
| record_format | Article |
| series | Endocrinology and Metabolism |
| spelling | doaj-art-65b4d63af43b44f0b59ab7a784899f2f2025-01-03T05:15:26ZengKorean Endocrine SocietyEndocrinology and Metabolism2093-596X2093-59782024-12-0139690892010.3803/EnM.2024.19842543Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial DysfunctionThuy Linh Lai0So Young Park1Giang Nguyen2Phuc Thi Minh Pham3Seon Mee Kang4Jeana Hong5Jae-Ho Lee6Seung-Soon Im7Dae-Hee Choi8Eun-Hee Cho9 Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea Department of Pediatrics, Kangwon National University School of Medicine, Chuncheon, Korea Department of Physiology, Keimyung University School of Medicine, Daegu, Korea Department of Physiology, Keimyung University School of Medicine, Daegu, Korea Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, KoreaBackground Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction. Methods In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days. Results In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson’s trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery. Conclusion Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.http://www.e-enm.org/upload/pdf/enm-2024-1984.pdfliver cirrhosisirisinhepatic stellate cellsmitochondriatransforming growth factor beta1 |
| spellingShingle | Thuy Linh Lai So Young Park Giang Nguyen Phuc Thi Minh Pham Seon Mee Kang Jeana Hong Jae-Ho Lee Seung-Soon Im Dae-Hee Choi Eun-Hee Cho Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction Endocrinology and Metabolism liver cirrhosis irisin hepatic stellate cells mitochondria transforming growth factor beta1 |
| title | Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction |
| title_full | Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction |
| title_fullStr | Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction |
| title_full_unstemmed | Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction |
| title_short | Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction |
| title_sort | irisin attenuates hepatic stellate cell activation and liver fibrosis in bile duct ligation mice model and improves mitochondrial dysfunction |
| topic | liver cirrhosis irisin hepatic stellate cells mitochondria transforming growth factor beta1 |
| url | http://www.e-enm.org/upload/pdf/enm-2024-1984.pdf |
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