Endocrinology and Metabolism

Original Articles

Diabetes, obesity and metabolism
Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction: 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; Endocrinol Metab. 2024;39(6):908-920. Published online November 5, 2024; DOI: https://doi.org/10.3803/EnM.2024.1984

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6 Crossref

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.

Citations

Citations to this article as recorded by

Targeting the Hepatic Stellate Cell Microenvironment: Nanomedicine Strategies for Liver Fibrosis Therapy
Lulu Pei, Xing Du, Zehao Mao, Kai Ding, Jiangyu Li, Tianqing Liu, Yongmei Zhao
Molecular Pharmaceutics.2026; 23(2): 662. CrossRef
Irisin Attenuates Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension via Ubiquitin‐Mediated Regulation of ENO1
Na Sun, Yong‐Bing Wang, Jing Huang, Run‐Wei Deng, Hui‐Yu He, Lei Gao, Xuan Gao, You‐Li Fan, Yan Cong, Yao‐Lei Guo, Yi‐Qiang Chen, Gui‐Jia Wang, Shao‐Hong Fang, Xia Gu, Bo Yu, Bing‐Xiang Wu
Advanced Science.2025;[Epub] CrossRef
The Influence of Irisin on Selected Organs—The Liver, Kidneys, and Lungs: The Role of Physical Exercise
Maria Ciałowicz, Marek Woźniewski, Eugenia Murawska-Ciałowicz, Piotr Dzięgiel
Cells.2025; 14(16): 1228. CrossRef
Metabolic and immune links between sarcopenia and liver disease
Stanislav Nikolaevich Kotlyarov
World Journal of Hepatology.2025;[Epub] CrossRef
Irisin, the Myokine: Guardian and Mediator in Cardiovascular System
Tian Lan, Xueru Yan, Jie Li, Haoran Gu, Qi Hou, Enpeng He, Qingyuan Yang
Endocrinology, Diabetes & Metabolism.2025;[Epub] CrossRef
Inflammation—Insulin Resistance Crosstalk and the Central Role of Myokines
Maria-Zinaida Dobre, Bogdana Virgolici, Daciana Costina Andrada Dunca-Stefan, Ioana-Cristina Doicin, Iulia-Ioana Stanescu-Spinu
International Journal of Molecular Sciences.2025; 27(1): 60. CrossRef

Endocrine Research
Irisin Regulates the Functions of Hepatic Stellate Cells: Hanh Nguyen Dong, So Young Park, Cong Thuc Le, Dae-Hee Choi, Eun-Hee Cho; Endocrinol Metab. 2020;35(3):647-655. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.658

10,475 View
206 Download
21 Web of Science
18 Crossref

Abstract PDF PubReader ePub

Background
Hepatic stellate cells (HSCs) are known to play a fundamental role in the progression of liver fibrosis. Once HSCs are activated, they are involved in proliferation, migration, and contractility which are characteristics of liver fibrogenesis. Recent studies have shown that irisin, a myokine secreted during physical exercise, has a protective effect in various metabolic diseases, especially in renal fibrosis. However, whether irisin is involved in HSC activation and other processes associated with liver fibrosis has not yet been investigated. In this study, we reveal the role of irisin in HSC activation as well as in proliferation, migration, and contractile properties of HSCs in vitro.
Methods
LX-2 cells, immortalized human HSCs, were treated with transforming growth factor beta 1 (TGF-β1), a core regulator of HSC fibrosis, with or without irisin, and markers of the aforementioned processes were analyzed. Further, an inflammatory response was stimulated with TGF-β1 and lipopolysaccharide (LPS) in combination with irisin and the expression of cytokines was measured.
Results
Recombinant irisin significantly suppressed the expression of TGF-β1-stimulated fibrosis markers including alpha-smooth muscle actin and collagen type 1 alpha 1 and prevented the TGF-β1-induced proliferation, migration, and contractility of LX-2 cells. Additionally, irisin ameliorated the production of interleukin-6 (IL-6) and IL-1β induced by TGF-β1 and LPS treatments.
Conclusion
These findings suggested that irisin potently improved the progression of hepatic fibrosis by regulating HSC activation, proliferation, migration, contractility, and HSC-mediated production of inflammatory cytokine.

Citations

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Tissue and Cell.2025; 95: 102829. CrossRef
Sarcopenia and metabolic dysfunction-associated steatotic liver disease: The role of exercise-related biomarkers
Marwan S Al-Nimer
World Journal of Hepatology.2025;[Epub] CrossRef
The Influence of Irisin on Selected Organs—The Liver, Kidneys, and Lungs: The Role of Physical Exercise
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Irisin Attenuates Hepatic Stellate Cell Activation and Liver Fibrosis in Bile Duct Ligation Mice Model and Improves Mitochondrial Dysfunction
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