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Hwan-Jin Hwang 2 Articles
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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
Endocrinol Metab. 2023;38(6):760-769.   Published online November 2, 2023
DOI: https://doi.org/10.3803/EnM.2023.1774
  • 2,435 View
  • 105 Download
  • 1 Web of Science
  • 2 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
G protein-coupled receptor 40 (GPR40) is a key molecule in diabetes and fatty liver, but its role in endothelial dysfunction remains unclear. Our objective in this study was to determine whether GPR40 agonists protect endothelial cells against palmitatemediated oxidative stress.
Methods
Human umbilical vein endothelial cells (HUVECs) were used to investigate effects of various GPR40 agonists on vascular endothelium.
Results
In HUVECs, AM1638, a GPR40-full agonist, enhanced nuclear factor erythroid 2–related factor 2 (NRF2) translocation to the nucleus and heme oxygenase-1 (HO-1) expression, which blocked palmitate-induced superoxide production. Those antioxidant effects were not detected after treatment with LY2922470 or TAK875, GPR40-partial agonists, suggesting that GPR40 regulates reactive oxygen species (ROS) removal in a ligand-dependent manner. We also found that palmitate-induced CCAAT/enhancer‐binding protein homologous protein expression; X-box binding protein-1 splicing, nuclear condensation, and fragmentation; and caspase-3 cleavage were all blocked in an NRF2-dependent manner after AM1638 treatment. Both LY2922470 and TAK875 also improved cell viability independent of the NRF2/ROS pathway by reducing palmitate-mediated endoplasmic reticulum stress and nuclear damage. GPR40 agonists thus have beneficial effects against palmitate in HUVECs. In particular, AM1638 reduced palmitate-induced superoxide production and cytotoxicity in an NRF2/HO-1 dependent manner.
Conclusion
GPR40 could be developed as a good therapeutic target to prevent or treat cardiovascular diseases such as atherosclerosis.

Citations

Citations to this article as recorded by  
  • From oxidative stress to metabolic dysfunction: The role of TRPM2
    Ying-Shuang Li, Hua-Cheng Ren, Hui Li, Man Xing, Jian-Hua Cao
    International Journal of Biological Macromolecules.2025; 284: 138081.     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
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Diabetes, Obesity and Metabolism
Sestrin2 Regulates Beneficial β3-Adrenergic Receptor-Mediated Effects Observed in Inguinal White Adipose Tissue and Soleus Muscle
Min Jeong Park, Joo Won Kim, Eun Roh, Kyung Mook Choi, Sei Hyun Baik, Hwan-Jin Hwang, Hye Jin Yoo
Endocrinol Metab. 2022;37(3):552-557.   Published online June 29, 2022
DOI: https://doi.org/10.3803/EnM.2022.1421
  • 3,300 View
  • 116 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Sestrin2, a well-known adenosine monophosphate-activated protein kinase (AMPK) regulator, plays a protective role against metabolic stress. The β3-adrenergic receptor (β3AR) induces fat browning and inhibits muscle atrophy in an AMPK-dependent manner. However, no prior research has examined the relationship of sestrin2 with β3AR in body composition changes. In this study, CL 316,243 (CL), a β3AR agonist, was administered to wild-type and sestrin2-knockout (KO) mice for 2 weeks, and fat and muscle tissues were harvested. CL induced AMPK phosphorylation, expression of brown-fat markers, and mitochondrial biogenesis, which resulted in the reduction of lipid droplet size in inguinal white adipose tissue (iWAT). These effects were not observed in sestrin2-KO mice. In CL-treated soleus muscle, sestrin2-KO was related to decreased myogenic gene expression and increased levels of muscle atrophy-related molecules. Our results suggest that sestrin2 is associated with beneficial β3AR-mediated changes in body composition, especially in iWAT and in the soleus.

Citations

Citations to this article as recorded by  
  • Sestrin2 levels in patients with anxiety and depression myocardial infarction was up-regulated and suppressed inflammation and ferroptosis by LKB1-mediated AMPK activation
    Yufeng Qian, Lian Chen, Beibei Gao, Xianhua Ye
    Clinical and Experimental Hypertension.2023;[Epub]     CrossRef
  • Sestrin2 in diabetes and diabetic complications
    Xiaodan Zhang, Zirui Luo, Jiahong Li, Yaxuan Lin, Yu Li, Wangen Li
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
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