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4 "Seung-Soon Im"
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Diabetes, obesity and metabolism
Progranulin Deficiency Improves Metabolic Stress Yet Falls Short of Sodium-Glucose Cotransporter-2 Inhibition in Autophagy-Linked Renal Protection
Seung-Soon Im
Endocrinol Metab. 2026;41(1):105-107.   Published online February 26, 2026
DOI: https://doi.org/10.3803/EnM.2026.2948
  • 1,316 View
  • 30 Download
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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
  • 6,969 View
  • 168 Download
  • 8 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   ePub   
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
  • From bench to bedside: Molecular mechanisms, diagnostic tools, and therapeutic strategies in liver fibrosis
    Zhen Yang, Weizhao Tong, Kanglong Zhang, Guoxin Hu
    Liver Research.2026; 10(2): 133.     CrossRef
  • SREBP2 links ACSS2-dependent acetyl-CoA biosynthesis to metaboloepigenetic activation of hepatic stellate cells and liver fibrosis
    Yu Wang, Aoqi Kang, Shunjie Wang, Zhen Yang, Hong Liu, Linbo Yue, Hao Li, Caiyi Wu, Wenjing Ren, Xiulian Miao, Zilong Li, Yong Xu, Zhiwen Fan
    Metabolism.2026; 179: 156597.     CrossRef
  • Synthesis and application of encapsulated Bifidobacterium Longum for mitigation of liver fibrosis via modulation of oxidative stress and inflammation in BDL rat model
    Siavash Amiri, Mitra Motallebi, Mohsen Hemmati-Dinarvand, Merat Karimi, Maryam Akhavan Taheri, Sahar Ahmadi Asouri, Mohammad Esmaeil Shahaboddin
    World Journal of Microbiology and Biotechnology.2026;[Epub]     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
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Diabetes, obesity and metabolism
Phloretin Ameliorates Succinate-Induced Liver Fibrosis by Regulating Hepatic Stellate Cells
Cong Thuc Le, Giang Nguyen, So Young Park, Hanh Nguyen Dong, Yun Kyung Cho, Jae-Ho Lee, Seung-Soon Im, Dae-Hee Choi, Eun-Hee Cho
Endocrinol Metab. 2023;38(4):395-405.   Published online August 3, 2023
DOI: https://doi.org/10.3803/EnM.2023.1661
  • 7,233 View
  • 144 Download
  • 5 Web of Science
  • 6 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
Hepatic stellate cells (HSCs) are the major cells which play a pivotal role in liver fibrosis. During injury, extracellular stimulators can induce HSCs transdifferentiated into active form. Phloretin showed its ability to protect the liver from injury, so in this research we would like to investigate the effect of phloretin on succinate-induced HSCs activation in vitro and liver fibrosis in vivo study.
Methods
In in vitro, succinate was used to induce HSCs activation, and then the effect of phloretin on activated HSCs was examined. In in vivo, succinate was used to generated liver fibrosis in mouse and phloretin co-treated to check its protection on the liver.
Results
Phloretin can reduce the increase of fibrogenic markers and inhibits the proliferation, migration, and contraction caused by succinate in in vitro experiments. Moreover, an upregulation of proteins associated with aerobic glycolysis occurred during the activation of HSCs, which was attenuated by phloretin treatment. In in vivo experiments, intraperitoneal injection of phloretin decreased expression of fibrotic and glycolytic markers in the livers of mice with sodium succinate diet-induced liver fibrosis. These results suggest that aerobic glycolysis plays critical role in activation of HSCs and succinate can induce liver fibrosis in mice, whereas phloretin has therapeutic potential for treating hepatic fibrosis.
Conclusion
Intraperitoneal injection of phloretin attenuated succinate-induced hepatic fibrosis and alleviates the succinate-induced HSCs activation.

Citations

Citations to this article as recorded by  
  • Succinate activates fibroblasts through GPR91-HIF-1α-TGF-β1-Smad signaling
    Ziyuan Zhang, Ziwen Wang, Haimei Sun, Deshan Zhou, Wei Ma
    Journal of Radiation Research and Applied Sciences.2026; 19(2): 102423.     CrossRef
  • Functional sweet tea in China: species, sweet components and anti-metabolic disease effects
    Zi-Yu Yan, Xi-Fan Wei, Gui-Ming Deng, Wen-Bo Yang, Rui Gui, Wen-Xuan Wang, Feng-Hua Kang, Jing Li, Yi-Heng Liu, Kang-Ping Xu, Yi-Kun Wang
    Frontiers in Nutrition.2026;[Epub]     CrossRef
  • The role of 8-OxoG and its repair systems in liver diseases progression: responsible mechanisms and promising natural products
    Ying Zheng, Junxin Chen, Ze Liu, Kaibo Wang, Hao Zhang
    Chinese Journal of Natural Medicines.2025; 23(7): 815.     CrossRef
  • Glycolysis to lactylation: Unraveling the metabolic and epigenetic landscape in tissue fibrosis (Review)
    Luna Zhang, Qianqian Li, Yuxin Deng, Yuanxia Zou, Li Wang, Jianchun Li
    Molecular Medicine Reports.2025; 32(5): 1.     CrossRef
  • The potential of flavonoids in hepatic fibrosis: A comprehensive review
    Zhu Wenbo, Han Jianwei, Liu Hua, Tang Lei, Chen Guijuan, Tian Mengfei
    Phytomedicine.2024; 133: 155932.     CrossRef
  • Advancements in Plant-Based Therapeutics for Hepatic Fibrosis: Molecular Mechanisms and Nanoparticulate Drug Delivery Systems
    Alina Ciceu, Ferenc Fenyvesi, Anca Hermenean, Simona Ardelean, Simona Dumitra, Monica Puticiu
    International Journal of Molecular Sciences.2024; 25(17): 9346.     CrossRef
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Review Article
Recent Insights into Insulin-Like Growth Factor Binding Protein 2 Transcriptional Regulation
Minsang Shin, Hye Suk Kang, Jae-Hyung Park, Jae-Hoon Bae, Dae-Kyu Song, Seung-Soon Im
Endocrinol Metab. 2017;32(1):11-17.   Published online January 19, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.1.11
  • 10,555 View
  • 92 Download
  • 32 Web of Science
  • 34 Crossref
AbstractAbstract PDFPubReader   

Insulin-like growth factor binding proteins (IGFBPs) are major regulators of insulin-like growth factor bioavailability and activity in metabolic signaling. Seven IGFBP family isoforms have been identified. Recent studies have shown that IGFBPs play a pivotal role in metabolic signaling and disease, including the pathogenesis of obesity, diabetes, and cancer. Although many studies have documented the various roles played by IGFBPs, transcriptional regulation of IGFBPs is not well understood. In this review, we focus on the regulatory mechanisms of IGFBP gene expression, and we summarize the findings of transcription factor activity in the IGFBP promoter region.

Citations

Citations to this article as recorded by  
  • Insulin-like growth factor binding protein 2 (IGFBP-2) as prognostic parameter in infarct-related cardiogenic shock
    Maryna Masyuk, Bernhard Wernly, Malte Kelm, Anne Freund, Janine Pöss, Steffen Desch, Steffen Schneider, Ibrahim Akin, Georg Fürnau, Uta Ceglarek, Mara Schemmelmann, Berend Isermann, Norbert Gerdes, Benedikt Schrage, Uwe Zeymer, Petra Büttner, Holger Thiel
    International Journal of Cardiology.2026; 443: 133961.     CrossRef
  • Immunogenetic and molecular biomarkers in COVID-19 and hepatitis C virus infection: Evaluating the diagnostic potential of HLA (rs1131500), IGF-2, and I-FABP
    Amal Ahmed Mohamed, Rasha M Abdel-Hamid, Amr Amin, Eman Al Hussain A Gawad, Salma Mohamed Saed, Dalia A Gaber, Mohamed Ezz Al Arab, Waleed El-Agawy, Mohammed Zakaria Ali AbuRahma, Heba Hanafy Elosaily, Elsaeed E Shaaban, Shaymaa A Ismail, Amany A Sakr
    World Journal of Hepatology.2026;[Epub]     CrossRef
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    Xiaoyu Song, Wentao Zhong, Hao Zheng, Xinyang Ou, Dongjin Zheng, Zhuo Li
    Frontiers in Nutrition.2026;[Epub]     CrossRef
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    Frontiers in Endocrinology.2026;[Epub]     CrossRef
  • Placental abundances of IGF1, IGF2, IGFBP2, IGF2R, and PPARα are associated with birth weight
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