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Hwan-Jin Hwang  (Hwang HJ) 2 Articles
Basic Research
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GPR40 Agonism Modulates Inflammatory Reactions in Vascular Endothelial Cells
Joo Won Kim, Eun Roh, Kyung Mook Choi, Hye Jin Yoo, Hwan-Jin Hwang, Sei Hyun Baik
Diabetes Metab J. 2022;46(3):506-511.   Published online January 24, 2022
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  • 235 Download
  • 8 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   ePub   
Endothelial dysfunction is strongly linked with inflammatory responses, which can impact cardiovascular disease. Recently, G protein-coupled receptor 40 (GPR40) has been investigated as a modulator of metabolic stress; however, the function of GPR40 in vascular endothelial cells has not been reported. We analyzed whether treatment of GPR40-specific agonists modulated the inflammatory responses in human umbilical vein endothelial cells (HUVECs). Treatment with LY2922470, a GPR40 agonist, significantly reduced lipopolysaccharide (LPS)-mediated nuclear factor-kappa B (NF-κB) phosphorylation and movement into the nucleus from the cytosol. However, treatment with another GPR40 agonist, TAK875, did not inhibit LPS-induced NF-κB activation. LPS treatment induced expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and attachment of THP-1 cells to HUVECs, which were all decreased by LY2922470 but not TAK875. Our results showed that ligand-dependent agonism of GPR40 is a promising therapeutic target for overcoming inflammatory reactions in the endothelium.


Citations to this article as recorded by  
  • Synthetic GPR40/FFAR1 agonists: An exhaustive survey on the most recent chemical classes and their structure-activity relationships
    Abhik Paul, Sourin Nahar, Pankaj Nahata, Arnab Sarkar, Avik Maji, Ajeya Samanta, Sanmoy Karmakar, Tapan Kumar Maity
    European Journal of Medicinal Chemistry.2024; 264: 115990.     CrossRef
  • Metabolite-sensing GPCRs in rheumatoid arthritis
    Xuezhi Yang, Wankang Zhang, Luping Wang, Yingjie Zhao, Wei Wei
    Trends in Pharmacological Sciences.2024; 45(2): 118.     CrossRef
  • Aloe emodin promotes mucosal healing by modifying the differentiation fate of enteroendocrine cells via regulating cellular free fatty acid sensitivity
    Weilian Bao, Jiaren Lyu, Guize Feng, Linfeng Guo, Dian Zhao, Keyuan You, Yang Liu, Haidong Li, Peng Du, Daofeng Chen, Xiaoyan Shen
    Acta Pharmaceutica Sinica B.2024;[Epub]     CrossRef
  • IGF-1 inhibits inflammation and accelerates angiogenesis via Ras/PI3K/IKK/NF-κB signaling pathways to promote wound healing
    Xin Zhang, Fei Hu, Jie Li, Lin Chen, Yu-fei Mao, Qiu-bo Li, Chen-yao Nie, Cai Lin, Jian Xiao
    European Journal of Pharmaceutical Sciences.2024; 200: 106847.     CrossRef
  • Free Fatty Acids and Free Fatty Acid Receptors: Role in Regulating Arterial Function
    Fengzhi Yu, Boyi Zong, Lili Ji, Peng Sun, Dandan Jia, Ru Wang
    International Journal of Molecular Sciences.2024; 25(14): 7853.     CrossRef
  • GPR40 deficiency worsens metabolic syndrome‐associated periodontitis in mice
    Yanchun Li, Zhongyang Lu, Cameron L. Kirkwood, Keith L. Kirkwood, Stephen A. Wank, Ai‐Jun Li, Maria F. Lopes‐Virella, Yan Huang
    Journal of Periodontal Research.2023; 58(3): 575.     CrossRef
  • Signaling pathways and intervention for therapy of type 2 diabetes mellitus
    Rong Cao, Huimin Tian, Yu Zhang, Geng Liu, Haixia Xu, Guocheng Rao, Yan Tian, Xianghui Fu
    MedComm.2023;[Epub]     CrossRef
  • G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice
    Yingyu Lu, Wanlu Zhou, Qinghua Cui, Chunmei Cui
    International Journal of Molecular Sciences.2023; 24(15): 12244.     CrossRef
  • AM1638, a GPR40-Full Agonist, Inhibited Palmitate- Induced ROS Production and Endoplasmic Reticulum Stress, Enhancing HUVEC Viability in an NRF2-Dependent Manner
    Hwan-Jin Hwang, Joo Won Kim, SukHwan Yun, Min Jeong Park, Eyun Song, Sooyeon Jang, Ahreum Jang, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo
    Endocrinology and Metabolism.2023; 38(6): 760.     CrossRef
  • Learn from failures and stay hopeful to GPR40, a GPCR target with robust efficacy, for therapy of metabolic disorders
    Hong-Ping Guan, Yusheng Xiong
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
Adipose Gene Expression Profiles Related to Metabolic Syndrome Using Microarray Analyses in Two Different Models
Hye Jin Yoo, Hwan-Jin Hwang, Tae Woo Jung, Ja Young Ryu, Ho Cheol Hong, Hae Yoon Choi, Sei Hyun Baik, Kyung Mook Choi
Diabetes Metab J. 2014;38(5):356-365.   Published online October 17, 2014
  • 4,412 View
  • 45 Download
  • 7 Web of Science
  • 7 Crossref
AbstractAbstract PDFPubReader   

Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist has a wide-ranging influence on multiple components of metabolic syndrome. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a useful animal model of metabolic syndrome. To determine genes related to metabolic syndrome, we examined overlapping genes that are simultaneously decreased by PPAR-γ agonists and increased in OLETF rats using microarrays in two different models.


In the first microarray analysis, PPAR-γ agonist-treated db/db mice were compared to standard diet-fed db/db mice. In the second microarray analysis, OLETF rats were compared to Long-Evans Tokushima Otsuka (LETO) rats (control of OLETF rats).


Among the overlapping genes, in the present study, we validated that lipocalin-2 expression was significantly decreased in the visceral adipose tissue of PPAR-γ agonist-treated db/db mice compared to standard diet-fed db/db mice and increased in OLETF rats compared to LETO rats using real time reverse transcription polymerase chain reaction. Furthermore, we showed for the first time that lipocalin-2 expression was significantly increased in the visceral adipose tissues of obese humans compared with nonobese humans. In addition, the expression level of lipocalin-2 in human visceral adipose tissue had a significant positive correlation with body mass index, serum interleukin-6, adipocyte fatty acid binding protein levels, and white blood cell count.


Lipocalin-2 was confirmed to be a significant adipokine affected by PPAR-γ agonist and obesity in the present study. Also, for the first time in human visceral adipose tissue, it was determined that the expression of lipocalin-2 from obese humans was significantly increased and correlated with circulating inflammatory markers.


Citations to this article as recorded by  
  • Lipocalin‐2—The myth of its expression and function
    Dahui Li, Wai Yan Sun, Bowen Fu, Aimin Xu, Yu Wang
    Basic & Clinical Pharmacology & Toxicology.2020; 127(2): 142.     CrossRef
  • Lipocalin-2 counteracts metabolic dysregulation in obesity and diabetes
    Ioanna Mosialou, Steven Shikhel, Na Luo, Peristera Ioanna Petropoulou, Konstantinos Panitsas, Brygida Bisikirska, Nyanza J. Rothman, Roxane Tenta, Bertrand Cariou, Matthieu Wargny, Elisabeth Sornay-Rendu, Thomas Nickolas, Mishaela Rubin, Cyrille B. Confav
    Journal of Experimental Medicine.2020;[Epub]     CrossRef
  • Metabolism and adult neurogenesis: Towards an understanding of the role of lipocalin-2 and iron-related oxidative stress
    Ana Catarina Ferreira, Nuno Sousa, João M. Bessa, João Carlos Sousa, Fernanda Marques
    Neuroscience & Biobehavioral Reviews.2018; 95: 73.     CrossRef
  • LH-21, A Peripheral Cannabinoid Receptor 1 Antagonist, Exerts Favorable Metabolic Modulation Including Antihypertensive Effect in KKAy Mice by Regulating Inflammatory Cytokines and Adipokines on Adipose Tissue
    Ziqi Dong, Hui Gong, Yadan Chen, Hong Wu, Jun Wu, Yinghong Deng, Xinmao Song
    Frontiers in Endocrinology.2018;[Epub]     CrossRef
  • Lipocalin 2 produces insulin resistance and can be upregulated by glucocorticoids in human adipose tissue
    Prasad G. Kamble, Maria J. Pereira, Cherno O. Sidibeh, Sam Amini, Magnus Sundbom, Joey Lau Börjesson, Jan W. Eriksson
    Molecular and Cellular Endocrinology.2016; 427: 124.     CrossRef
  • Serum lipocalin-2 levels are positively associated with not only total body fat but also visceral fat area in Chinese men
    Yuqi Luo, Xiaojing Ma, Xiaoping Pan, Yiting Xu, Qin Xiong, Yunfeng Xiao, Yuqian Bao, Weiping Jia
    Medicine.2016; 95(30): e4039.     CrossRef
  • From the periphery to the brain: Lipocalin-2, a friend or foe?
    Ana C. Ferreira, Sandro Dá Mesquita, João C. Sousa, Margarida Correia-Neves, Nuno Sousa, Joana A. Palha, Fernanda Marques
    Progress in Neurobiology.2015; 131: 120.     CrossRef

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