Identification of a 2-phenoxychromone derivative as a novel inhibitor of lipid droplet formation in hepatocytes and adipocytes
Dysregulated lipid droplet (LD) accumulation in hepatocytes increases the risk of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide. Furthermore, excessive accumulation of LD...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | Results in Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715625003728 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849397107892420608 |
|---|---|
| author | Yu-Tsen Hsieh Tung-Hsuan Kang Hsin-Yi Hung Yi-Han Chang Kuan-Chen Cheng Chia-Yih Wang Wen-Tai Chiu Pai-Sheng Chen Shih-Chieh Lin I-Chen Peng |
| author_facet | Yu-Tsen Hsieh Tung-Hsuan Kang Hsin-Yi Hung Yi-Han Chang Kuan-Chen Cheng Chia-Yih Wang Wen-Tai Chiu Pai-Sheng Chen Shih-Chieh Lin I-Chen Peng |
| author_sort | Yu-Tsen Hsieh |
| collection | DOAJ |
| description | Dysregulated lipid droplet (LD) accumulation in hepatocytes increases the risk of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide. Furthermore, excessive accumulation of LD in adipocytes leads to obesity, insulin resistance, and metabolic complications, including MASLD. Therefore, there is a need to develop pharmacological inhibitors for reducing LD accumulation in hepatocytes and adipocytes. In this study, we used HepG2 and 3T3-L1 cells to investigate the LD-inhibiting effects of a 2-phenoxychromone derivative, 7-methoxy-2-(3′,4′,5′-trimethoxyphenoxy)-chromen-4-one (compound N4). Compound N4 repressed LD accumulation induced by oleic acid (OA) and linoleic acid (LA) in HepG2 cells with IC50 values of 44.5 ± 7.1 μM and 52 ± 11.8 μM, respectively. Compound N4 showed no significant cell cytotoxicity with a CC50 value of 293.7 ± 12.9 μM in HepG2 cells. Mechanistically, compound N4 inhibited LD formation induced by OA through reducing acetyl-CoA carboxylase 1 (ACC1), sterol regulatory element-binding protein 1 (SREBP1), cluster of differentiation 36 (CD36), and diacylglycerol O-acyltransferase 2 (DGAT2) mRNA expression. Moreover, compound N4 inhibited LD accumulation induced by LA through reducing CD36 and DGAT2 mRNA expression. Compound N4 also decreased LD formation and adipogenesis with an IC50 value of 35.9 ± 6.5 μM in 3T3-L1 cells. Compound N4 displayed no significant cell cytotoxicity with a CC50 value of 42.6 ± 3.2 μM, and it inhibited LD accumulation through reducing ACC1, SREBP1, CD36, DGAT2, CCAAT/enhancer binding protein α/β, and peroxisome proliferator-activated receptor γ mRNA expression in 3T3-L1 cells. Based on these findings, we identify compound N4 as a novel LD inhibitor in hepatocytes and adipocytes, which can be developed further for managing MASLD and obesity. |
| format | Article |
| id | doaj-art-dce3880c689f41709bcffd1f64a93be2 |
| institution | Kabale University |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj-art-dce3880c689f41709bcffd1f64a93be22025-08-20T03:39:09ZengElsevierResults in Chemistry2211-71562025-07-011610238910.1016/j.rechem.2025.102389Identification of a 2-phenoxychromone derivative as a novel inhibitor of lipid droplet formation in hepatocytes and adipocytesYu-Tsen Hsieh0Tung-Hsuan Kang1Hsin-Yi Hung2Yi-Han Chang3Kuan-Chen Cheng4Chia-Yih Wang5Wen-Tai Chiu6Pai-Sheng Chen7Shih-Chieh Lin8I-Chen Peng9Department of Life Sciences, National Cheng Kung University, Tainan City 701, TaiwanDepartment of Life Sciences, National Cheng Kung University, Tainan City 701, TaiwanSchool of Pharmacy and Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, TaiwanSchool of Pharmacy and Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, TaiwanInstitute of Food Science and Technology, National Taiwan University, Taipei 106, Taiwan; Department of Optometry, Asia University, 500, Lioufeng Rd., Wufeng, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, 91, Hsueh-Shih Road, Taichung, TaiwanDepartment of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, TaiwanDepartment of Biomedical Engineering, National Cheng Kung University, Tainan City 701, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, TaiwanDepartment of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan City 701, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 701, TaiwanDepartment of Life Sciences, National Cheng Kung University, Tainan City 701, Taiwan; Corresponding author.Dysregulated lipid droplet (LD) accumulation in hepatocytes increases the risk of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide. Furthermore, excessive accumulation of LD in adipocytes leads to obesity, insulin resistance, and metabolic complications, including MASLD. Therefore, there is a need to develop pharmacological inhibitors for reducing LD accumulation in hepatocytes and adipocytes. In this study, we used HepG2 and 3T3-L1 cells to investigate the LD-inhibiting effects of a 2-phenoxychromone derivative, 7-methoxy-2-(3′,4′,5′-trimethoxyphenoxy)-chromen-4-one (compound N4). Compound N4 repressed LD accumulation induced by oleic acid (OA) and linoleic acid (LA) in HepG2 cells with IC50 values of 44.5 ± 7.1 μM and 52 ± 11.8 μM, respectively. Compound N4 showed no significant cell cytotoxicity with a CC50 value of 293.7 ± 12.9 μM in HepG2 cells. Mechanistically, compound N4 inhibited LD formation induced by OA through reducing acetyl-CoA carboxylase 1 (ACC1), sterol regulatory element-binding protein 1 (SREBP1), cluster of differentiation 36 (CD36), and diacylglycerol O-acyltransferase 2 (DGAT2) mRNA expression. Moreover, compound N4 inhibited LD accumulation induced by LA through reducing CD36 and DGAT2 mRNA expression. Compound N4 also decreased LD formation and adipogenesis with an IC50 value of 35.9 ± 6.5 μM in 3T3-L1 cells. Compound N4 displayed no significant cell cytotoxicity with a CC50 value of 42.6 ± 3.2 μM, and it inhibited LD accumulation through reducing ACC1, SREBP1, CD36, DGAT2, CCAAT/enhancer binding protein α/β, and peroxisome proliferator-activated receptor γ mRNA expression in 3T3-L1 cells. Based on these findings, we identify compound N4 as a novel LD inhibitor in hepatocytes and adipocytes, which can be developed further for managing MASLD and obesity.http://www.sciencedirect.com/science/article/pii/S22117156250037282-phenoxychromone derivativeAdipocytesHepatocytesLipid dropletMetabolic dysfunction-associated steatotic liver diseaseObesity |
| spellingShingle | Yu-Tsen Hsieh Tung-Hsuan Kang Hsin-Yi Hung Yi-Han Chang Kuan-Chen Cheng Chia-Yih Wang Wen-Tai Chiu Pai-Sheng Chen Shih-Chieh Lin I-Chen Peng Identification of a 2-phenoxychromone derivative as a novel inhibitor of lipid droplet formation in hepatocytes and adipocytes Results in Chemistry 2-phenoxychromone derivative Adipocytes Hepatocytes Lipid droplet Metabolic dysfunction-associated steatotic liver disease Obesity |
| title | Identification of a 2-phenoxychromone derivative as a novel inhibitor of lipid droplet formation in hepatocytes and adipocytes |
| title_full | Identification of a 2-phenoxychromone derivative as a novel inhibitor of lipid droplet formation in hepatocytes and adipocytes |
| title_fullStr | Identification of a 2-phenoxychromone derivative as a novel inhibitor of lipid droplet formation in hepatocytes and adipocytes |
| title_full_unstemmed | Identification of a 2-phenoxychromone derivative as a novel inhibitor of lipid droplet formation in hepatocytes and adipocytes |
| title_short | Identification of a 2-phenoxychromone derivative as a novel inhibitor of lipid droplet formation in hepatocytes and adipocytes |
| title_sort | identification of a 2 phenoxychromone derivative as a novel inhibitor of lipid droplet formation in hepatocytes and adipocytes |
| topic | 2-phenoxychromone derivative Adipocytes Hepatocytes Lipid droplet Metabolic dysfunction-associated steatotic liver disease Obesity |
| url | http://www.sciencedirect.com/science/article/pii/S2211715625003728 |
| work_keys_str_mv | AT yutsenhsieh identificationofa2phenoxychromonederivativeasanovelinhibitoroflipiddropletformationinhepatocytesandadipocytes AT tunghsuankang identificationofa2phenoxychromonederivativeasanovelinhibitoroflipiddropletformationinhepatocytesandadipocytes AT hsinyihung identificationofa2phenoxychromonederivativeasanovelinhibitoroflipiddropletformationinhepatocytesandadipocytes AT yihanchang identificationofa2phenoxychromonederivativeasanovelinhibitoroflipiddropletformationinhepatocytesandadipocytes AT kuanchencheng identificationofa2phenoxychromonederivativeasanovelinhibitoroflipiddropletformationinhepatocytesandadipocytes AT chiayihwang identificationofa2phenoxychromonederivativeasanovelinhibitoroflipiddropletformationinhepatocytesandadipocytes AT wentaichiu identificationofa2phenoxychromonederivativeasanovelinhibitoroflipiddropletformationinhepatocytesandadipocytes AT paishengchen identificationofa2phenoxychromonederivativeasanovelinhibitoroflipiddropletformationinhepatocytesandadipocytes AT shihchiehlin identificationofa2phenoxychromonederivativeasanovelinhibitoroflipiddropletformationinhepatocytesandadipocytes AT ichenpeng identificationofa2phenoxychromonederivativeasanovelinhibitoroflipiddropletformationinhepatocytesandadipocytes |