Endocrinology and Metabolism

Original Articles

Diabetes, Obesity and Metabolism
The Effects of Irisin on the Interaction between Hepatic Stellate Cell and Macrophage in Liver Fibrosis: Dinh Vinh Do, So Young Park, Giang Thi Nguyen, Dae Hee Choi, Eun-Hee Cho; Endocrinol Metab. 2022;37(4):620-629. Published online July 22, 2022; DOI: https://doi.org/10.3803/EnM.2022.1412

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Background
Hepatic stellate cells (HSCs) are the central players interacting with multiple cell types in liver fibrosis. The crosstalk between HSCs and macrophages has recently become clearer. Irisin, an exercise-responsive myokine, was known to have a potentially protective role in liver and renal fibrosis, especially in connection with stellate cells. This study investigated the effects of irisin on the interaction between HSCs and macrophages.
Methods
Tamm-Horsfall protein-1 (THP-1) human monocytes were differentiated into macrophages, polarized into the inflammatory M1 phenotype with lipopolysaccharide. Lieming Xu-2 (LX-2) cells, human HSCs, were treated with conditioned media (CM) from M1 macrophages, with or without recombinant irisin. HSCs responses to CM from M1 macrophages were evaluated regarding activation, proliferation, wound healing, trans-well migration, contractility, and related signaling pathway.
Results
CM from M1 macrophages significantly promoted HSC proliferation, wound healing, transwell migration, and contractility, but not activation of HSCs. Irisin co-treatment attenuated these responses of HSCs to CM. However, CM and irisin treatment did not induce any changes in HSC activation. Further, irisin co-treatment alleviated CM-induced increase of phopho-protein kinase B (pAKT), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1).
Conclusion
These findings suggested that irisin may play a protective role in the pathogenesis of liver fibrosis, especially when working in the crosstalk between HSCs and macrophages.

Citations

Citations to this article as recorded by

Matrix metalloproteinases induce extracellular matrix degradation through various pathways to alleviate hepatic fibrosis
Liang Shan, Fengling Wang, Dandan Zhai, Xiangyun Meng, Jianjun Liu, Xiongwen Lv
Biomedicine & Pharmacotherapy.2023; 161: 114472. CrossRef
Potential role of irisin in digestive system diseases
Yueming Zhang, Linxian Zhao, Huan Gao, Jinghui Zhai, Yanqing Song
Biomedicine & Pharmacotherapy.2023; 166: 115347. CrossRef
The effect of sarcopenia and serum myokines on prognosis and survival in cirrhotic patients: a multicenter cross-sectional study
Salih Boga, Abdullah Emre Yildirim, Enver Ucbilek, Ali Riza Koksal, Sevil Tokdemir Sisman, Ibrahim Durak, Ilker Sen, Beril Dogu, Erdinc Serin, Ayse Bolat Ucbilek, Makbule Ozge Yildirim, Sukru Mehmet Erturk, Huseyin Alkim, Canan Alkim
European Journal of Gastroenterology & Hepatology.2022; 34(12): 1261. 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

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180 Download
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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

Citations to this article as recorded by

Potential role of irisin in digestive system diseases
Yueming Zhang, Linxian Zhao, Huan Gao, Jinghui Zhai, Yanqing Song
Biomedicine & Pharmacotherapy.2023; 166: 115347. CrossRef
Potential role of irisin in lung diseases and advances in research
Hongna Dong, Xuejiao Lv, Peng Gao, Yuqiu Hao
Frontiers in Pharmacology.2023;[Epub] CrossRef
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Journal of Investigative Medicine.2022; 70(5): 1285. CrossRef
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Yan-fang Deng, Qian-qian Xu, Tian-qi Chen, Jia-xiong Ming, Ya-fen Wang, Li-na Mao, Jia-jun Zhou, Wei-guang Sun, Qun Zhou, Hong Ren, Yong-hui Zhang
Phytomedicine.2022; 104: 154241. CrossRef
The potential role of FNDC5/irisin in various liver diseases: awakening the sleeping beauties
Xiaoyu Wang, Lihong Mao, Chaoqun Li, Yangyang Hui, Zihan Yu, Mingyu Sun, Yifan Li, Gaoyue Guo, Wanting Yang, Binxin Cui, Xiaofei Fan, Chao Sun
Expert Reviews in Molecular Medicine.2022;[Epub] CrossRef
The Effects of Irisin on the Interaction between Hepatic Stellate Cell and Macrophage in Liver Fibrosis
Dinh Vinh Do, So Young Park, Giang Thi Nguyen, Dae Hee Choi, Eun-Hee Cho
Endocrinology and Metabolism.2022; 37(4): 620. CrossRef
Hepatic Steatosis Contributes to the Development of Muscle Atrophy via Inter-Organ Crosstalk
Kenneth Pasmans, Michiel E. Adriaens, Peter Olinga, Ramon Langen, Sander S. Rensen, Frank G. Schaap, Steven W. M. Olde Damink, Florian Caiment, Luc J. C. van Loon, Ellen E. Blaak, Ruth C. R. Meex
Frontiers in Endocrinology.2021;[Epub] CrossRef
Physiopathology of Lifestyle Interventions in Non-Alcoholic Fatty Liver Disease (NAFLD)
David Carneros, Guillermo López-Lluch, Matilde Bustos
Nutrients.2020; 12(11): 3472. CrossRef

Clinical Study
Association between Circulating Irisin and C-Reactive Protein Levels: A Systematic Review and Meta-Analysis: Elham Eslampour, Farzad Ebrahimzadeh, Amir Abbasnezhad, Mohammad Zeinali Khosroshahi, Razieh Choghakhori, Omid Asbaghi; Endocrinol Metab. 2019;34(2):140-149. Published online June 24, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.2.140

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Background

Although previous studies have demonstrated that irisin plays an anti-inflammatory role in the body, conflicting results have been reported regarding the correlation between serum levels of irisin and C-reactive protein (CRP). The present meta-analysis was conducted to further investigate the correlation between irisin and CRP levels.

Methods

We systematically searched PubMed, the Cochrane Library, Web of Science, Embase, SCOPUS, and Ovid to retrieve studies assessing the correlation between irisin and CRP levels. Meta-analyses were performed using a random-effects model, and the I² index was used to evaluate heterogeneity.

Results

Of the 428 studies that were initially found, 14 studies with 2,530 participants met the inclusion criteria for the meta-analysis. The pooled effect size was calculated as 0.052 (95% confidence interval, −0.047 to 0.152; P=0.302). Subgroup analyses identified s ignificant, positive, but weak correlations between CRP and irisin levels in cohort studies, studies conducted among healthy participants, studies in which the male-to-female ratio was less than 1, in overweight or obese subjects, and in studies with a sample size of at least 100 participants.

Conclusion

The present meta-analysis found no overall significant correlation between irisin and CRP levels, although a significant positive correlation was found in overweight or obese subjects. Well-designed studies are needed to verify the results of the present meta-analysis.

Citations

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Zinc Supplementation in Individuals with Prediabetes and type 2 Diabetes: a GRADE-Assessed Systematic Review and Dose-Response Meta-analysis
Matin Nazari, Mahlagha Nikbaf-Shandiz, Fereshteh Pashayee-Khamene, Reza Bagheri, Kian Goudarzi, Navid Vahid Hosseinnia, Sina Dolatshahi, Hossein Salehi Omran, Niusha Amirani, Damoon Ashtary-larky, Omid Asbaghi, Matin Ghanavati
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Irisin reduces inflammatory signaling pathways in inflammation-mediated metabolic syndrome
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Molecular and Cellular Endocrinology.2022; 552: 111676. CrossRef
Circulating Irisin Levels in Patients with Chronic Plaque Psoriasis
Francesca Ambrogio, Lorenzo Sanesi, Angela Oranger, Chiara Barlusconi, Manuela Dicarlo, Patrizia Pignataro, Roberta Zerlotin, Paolo Romita, Elvira Favoino, Gerardo Cazzato, Nicoletta Cassano, Gino Antonio Vena, Caterina Foti, Maria Grano
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Xin Zhang, Can Hu, Hai-ming Wu, Zhen-guo Ma, Qi-zhu Tang
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Progress and Challenges in the Biology of FNDC5 and Irisin
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L-arginine supplementation to mitigate cardiovascular effects of walking outside in the context of traffic-related air pollution in participants with elevated blood pressure: A randomized, double-blind, placebo-controlled trial
Hongyu Li, Qisijing Liu, Zhiyong Zou, Qiao Chen, Wanzhou Wang, Andrea A. Baccarelli, Furong Deng, Xinbiao Guo, Shaowei Wu
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Effect of ursodeoxycholic acid therapy due to pregnant intrahepatic cholestasis on chemerin and irisin levels
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The effects of royal jelly and tocotrienol‐rich fraction on impaired glycemic control and inflammation through irisin in obese rats
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Journal of Food Biochemistry.2020;[Epub] CrossRef
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Review Article

Obesity and Metabolism
Novel Molecules Regulating Energy Homeostasis: Physiology and Regulation by Macronutrient Intake and Weight Loss: Anna Gavrieli, Christos S. Mantzoros; Endocrinol Metab. 2016;31(3):361-372. Published online July 26, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.3.361

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Abstract PDF PubReader

Excess energy intake, without a compensatory increase of energy expenditure, leads to obesity. Several molecules are involved in energy homeostasis regulation and new ones are being discovered constantly. Appetite regulating hormones such as ghrelin, peptide tyrosine-tyrosine and amylin or incretins such as the gastric inhibitory polypeptide have been studied extensively while other molecules such as fibroblast growth factor 21, chemerin, irisin, secreted frizzle-related protein-4, total bile acids, and heme oxygenase-1 have been linked to energy homeostasis regulation more recently and the specific role of each one of them has not been fully elucidated. This mini review focuses on the above mentioned molecules and discusses them in relation to their regulation by the macronutrient composition of the diet as well as diet-induced weight loss.

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