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The potential role of FNDC5/irisin in various liver diseases: awakening the sleeping beauties

Published online by Cambridge University Press:  13 June 2022

Xiaoyu Wang ,
Lihong Mao ,
Chaoqun Li ,
Yangyang Hui ,
Zihan Yu ,
Mingyu Sun ,
Yifan Li ,
Gaoyue Guo ,
Wanting Yang  and
Binxin Cui
...Show all authors
Xiaoyu Wang
Affiliation:
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Lihong Mao
Affiliation:
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Chaoqun Li
Affiliation:
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China Department of Internal Medicine, Tianjin Hexi Hospital, Qiongzhou Road 43, Hexi District, Tianjin 300202, China
Yangyang Hui
Affiliation:
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Zihan Yu
Affiliation:
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Mingyu Sun
Affiliation:
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Yifan Li
Affiliation:
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Gaoyue Guo
Affiliation:
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Wanting Yang
Affiliation:
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Binxin Cui
Affiliation:
Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin 300308, China
Xiaofei Fan
Affiliation:
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China
Chao Sun*
Affiliation:
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China Tianjin Institute of Digestive Disease, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin 300052, China Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin 300308, China
*
Author for correspondence: Chao Sun, E-mail: chaosun@tmu.edu.cn
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Abstract

Fibronectin type III domain-containing protein 5 (FNDC5) is a transmembrane protein and the precursor of irisin, which serves as a systemic exerkine/myokine with multiple origins. Since its discovery in 2012, this hormone-like polypeptide has rapidly evolved to a component significantly involved in a gamut of metabolic dysregulations and various liver diseases. After a decade of extensive investigation on FNDC5/irisin, we are still surrounded by lots of open questions regarding its diagnostic and therapeutic values. In this review, we first concentrated on the structure–function relationship of FNDC5/irisin. Next, we comprehensively summarised the current knowledge and research findings regarding pathogenic roles/therapeutic applications of FNDC5/irisin in the context of non-alcoholic fatty liver disease, fibrosis, liver injury due to multiple detrimental insults, hepatic malignancy and intrahepatic cholestasis of pregnancy. Moreover, the prominent molecules involved in the underlying mechanisms and signalling pathways were highlighted. As a result, emerging evidence reveals FNDC5/irisin may act as a proxy for diagnosing liver disease pathology, a sensitive biomarker for assessing damage severity, a predisposing factor for surveilling illness progression and a treatment option with protective/preventive impact, all of which are highly dependent on disease grading and contextually pathological features.

Keywords

AMPKbiomarkerFNDC5irisinliver diseasenon-alcoholic fatty liver diseasePGC1α

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Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 24 , 2022 , e23
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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Footnotes

*

These authors have contributed equally to this work and share first authorship.

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