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

Wang, Xiaoyu; Mao, Leilei; Li, Chaoqun; Hui, Yangyang; Yu, Zihan; Sun, Mingyu; Li, Yifan; Guo, Gaoyue; Yang, Wanting; Cui, Binxin; Fan, Xiaofei; Sun, Chao

doi:10.1017/erm.2022.19

Cited by 5 publications

(2 citation statements)

References 130 publications

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“…It has been reported that irisin plays important roles in regulating energy metabolism, insulin resistance, oxidative stress, inflammation, cell apoptosis, and fibrosis [ 26 , 27 , 28 ]. FNDC5/irisin is involved in different types of liver diseases, such as NAFLD, multiple detrimental insults-induced liver injury, and hepatic malignancy [ 29 ]. However, little is known about the effect of irisin on MI-induced liver injury.…”

Section: Introductionmentioning

confidence: 99%

FNDC5/Irisin Inhibits the Inflammatory Response and Mediates the Aerobic Exercise-Induced Improvement of Liver Injury after Myocardial Infarction

Wang

et al. 2023

IJMS

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Myocardial infarction (MI) causes peripheral organ injury, in addition to cardiac dysfunction, including in the liver, which is known as cardiac hepatopathy. Aerobic exercise (AE) can effectively improve liver injury, although the mechanism and targets are currently not well established. Irisin, mainly produced by cleavage of the fibronectin type III domain-containing protein 5 (FNDC5), is a responsible for the beneficial effects of exercise training. In this study, we detected the effect of AE on MI-induced liver injury and explored the role of irisin alongside the benefits of AE. Wildtype and Fndc5 knockout mice were used to establish an MI model and subjected to AE intervention. Primary mouse hepatocytes were treated with lipopolysaccharide (LPS), rhirisin, and a phosphoinositide 3-kinase (PI3K) inhibitor. The results showed that AE significantly promoted M2 polarization of macrophages and improved MI-induced inflammation, upregulated endogenous irisin protein expression and activated the PI3K/ protein kinase B (Akt) signaling pathway in the liver of MI mice, while knockout of Fndc5 attenuated the beneficial effects of AE. Exogenous rhirisin significantly inhibited the LPS-induced inflammatory response, which was attenuated by the PI3K inhibitor. These results suggest that AE could effectively activate the FNDC5/irisin-PI3K/Akt signaling pathway, promote the polarization of M2 macrophages, and inhibit the inflammatory response of the liver after MI.

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Section: Introductionmentioning

confidence: 99%

FNDC5/Irisin Inhibits the Inflammatory Response and Mediates the Aerobic Exercise-Induced Improvement of Liver Injury after Myocardial Infarction

Wang

et al. 2023

IJMS

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“…This is linked with the necessity of identifying the causes leading to the excessive accumulation of lipids in the liver. An increasing number of studies have indicated an etiological relationship between NAFLD and irisin concentration [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Irisin Is Related to Non-Alcoholic Fatty Liver Disease (NAFLD)

et al. 2022

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Irisin is a cytokine involved in many metabolic pathways occurring, among others, in muscles, adipose tissue and liver. Thus, fluctuations in irisin levels are suggested to be related to metabolic diseases. Therefore, the purpose of our study was to evaluate whether irisin may be associated with non-alcoholic fatty liver disease (NAFLD). A total of 138 patients (70/68 male/female, mean age 65.61 ± 10.44 years) were enrolled in the study. The patients were assigned to the NAFLD group (n = 72, including 46 patients with type 2 diabetes (T2DM]) and the group without NAFLD (n = 66, 31 patients with T2DM). NAFLD was diagnosed based on ultrasound examination, Hepatic Steatosis Index (HSI) and Fatty Liver Index. Baseline anthropometric, blood pressure and biochemical parameters were collected. The serum irisin level was determined using an ELISA test. We observed that NAFLD was associated with an increased concentration of irisin. Moreover, Spearman correlations and linear regression analysis revealed that irisin level correlates with some anthropometric and biochemical parameters such as body mass index, glycated hemoglobin, aspartic aminotransferase, creatinine and urea. Logistic regression analysis depicted that odds for NAFLD increase 1.17 times for each 1 μg/mL rise of irisin concentration. Finally, ROC analysis showed that the concentration of irisin possesses a discriminate capacity for NAFLD and optimal cut points concentration could be designed. The risk of NAFLD in the subgroup with irisin concentration above 3.235 μg/mL was 4.57 times higher than in patients with the lower concentration of irisin. To conclude, the obtained results suggest that irisin concentration is associated with some anthropometric and biochemical parameters and should be further investigated toward its usage as a diagnostic biomarker of NAFLD.

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Potential mechanisms of rheumatoid arthritis therapy: Focus on macrophage polarization

Yang,

Li,

et al. 2024

International Immunopharmacology

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

Cited by 5 publications

References 130 publications

FNDC5/Irisin Inhibits the Inflammatory Response and Mediates the Aerobic Exercise-Induced Improvement of Liver Injury after Myocardial Infarction

FNDC5/Irisin Inhibits the Inflammatory Response and Mediates the Aerobic Exercise-Induced Improvement of Liver Injury after Myocardial Infarction

Irisin Is Related to Non-Alcoholic Fatty Liver Disease (NAFLD)

Potential mechanisms of rheumatoid arthritis therapy: Focus on macrophage polarization

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