Diabetes & Metabolism Journal

Hwan-Jin Hwang (Hwang HJ)

2 Articles

Basic Research
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; DOI: https://doi.org/10.4093/dmj.2021.0092

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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

Citations to this article as recorded by

Type 2 Diabetes Mellitus: A Comprehensive Review of Pathophysiology, Comorbidities, and Emerging Therapies
Aditi Singh, Sucharita Shadangi, Pulkit Kr. Gupta, Soumendra Rana
Comprehensive Physiology.2025;[Epub] CrossRef
GPR40-full agonist AM1638 alleviates palmitate-induced oxidative damage in H9c2 cells via an AMPK-dependent pathway
SukHwan Yun, Joo Won Kim, Min Jeong Park, Eyun Song, Soo Yeon Jang, Ahreum Jang, Kyung Mook Choi, Sei Hyun Baik, Hwan-Jin Hwang, Hye Jin Yoo
BMB Reports.2025; 58(3): 133. CrossRef
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; 14(9): 3964. 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
Critical role of G protein-coupled receptor 40 in B cell response and the pathogenesis of rheumatoid arthritis in mice and patients
Anqi Li, Xiaoyi Wang, Jingwen Li, Xiaoyu Li, Jue Wang, Yang Liu, Zhihong Wang, Xiaobing Yang, Jiapeng Gao, Juanjie Wu, Tao Sun, Lixia Huo, Yanfeng Yi, Jiantong Shen, Jiexun Cai, Yunliang Yao
Cell Reports.2024; 43(10): 114858. CrossRef
Recent Developments in Drug Design of Oral Synthetic Free Fatty Acid Receptor 1 Agonists
Lei Liu, Qinghua Zhang, Yichuan Ma, Ling Lin, Wenli Liu, Aizhong Ding, Chunjian Wang, Shuiping Zhou, Jinyong Cai, Hai Tang
Drug Design, Development and Therapy.2024; Volume 18: 5961. 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; DOI: https://doi.org/10.4093/dmj.2014.38.5.356

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Abstract PDF PubReader

Background

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.

Methods

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).

Results

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.

Conclusion

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

Citations to this article as recorded by

Lipocalin‐2—The myth of its expression and function
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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
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