6-Gingerol regulates triglyceride and cholesterol biosynthesis to improve hepatic steatosis in MAFLD by activating the AMPK-SREBPs signaling pathway
Excessive synthesis of triglycerides and cholesterol accelerates the progression of hepatic steatosis in metabolic-associated fatty liver disease (MAFLD). However, the precise mechanism by which 6-gingerol mitigates hepatic steatosis in MAFLD model mice has yet to be fully understood. The present st...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223018589 |
| _version_ | 1797364247866376192 |
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| author | Qingsong Xia Fuer Lu Yu Chen Jingbin Li Zhaoyi Huang Ke Fang Meilin Hu Yujin Guo Hui Dong Lijun Xu Jing Gong |
| author_facet | Qingsong Xia Fuer Lu Yu Chen Jingbin Li Zhaoyi Huang Ke Fang Meilin Hu Yujin Guo Hui Dong Lijun Xu Jing Gong |
| author_sort | Qingsong Xia |
| collection | DOAJ |
| description | Excessive synthesis of triglycerides and cholesterol accelerates the progression of hepatic steatosis in metabolic-associated fatty liver disease (MAFLD). However, the precise mechanism by which 6-gingerol mitigates hepatic steatosis in MAFLD model mice has yet to be fully understood. The present study observed that 6-gingerol administration exhibited significant protective effects against obesity, insulin resistance, and hepatic steatosis in mice subjected to a high-fat diet (HFD), and mitigated lipid accumulation in HepG2 cells treated with palmitate (PA). Following the hepatic lipidomic analysis, we confirmed that the AMPK-SREBPs signaling pathway as the underlying molecular mechanism by which 6-gingerol inhibited triglyceride and cholesterol biosynthesis, both in vivo and in vitro, through Western blot and immunofluorescence assay. Additionally, the application of an AMPK agonist/inhibitor further validated that 6-gingerol promoted AMPK activation by increasing the phosphorylation level of AMPK in vitro. Notably, the inhibitory effect of 6-gingerol on cholesterol biosynthesis, rather than triglyceride biosynthesis, was significantly diminished after silencing SREBP2 using a lentiviral plasmid shRNA in HepG2 cells. Our study demonstrates that 6-gingerol mitigates hepatic triglyceride and cholesterol biosynthesis to alleviate hepatic steatosis by activating the AMPK-SREBPs signaling pathway, indicating that 6-gingerol may be a potential candidate in the therapy of MAFLD. |
| first_indexed | 2024-03-08T16:33:33Z |
| format | Article |
| id | doaj.art-b387effc22304be49c6b34a4a5639989 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-08T16:33:33Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-b387effc22304be49c6b34a4a56399892024-01-06T04:38:07ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-01-011701160606-Gingerol regulates triglyceride and cholesterol biosynthesis to improve hepatic steatosis in MAFLD by activating the AMPK-SREBPs signaling pathwayQingsong Xia0Fuer Lu1Yu Chen2Jingbin Li3Zhaoyi Huang4Ke Fang5Meilin Hu6Yujin Guo7Hui Dong8Lijun Xu9Jing Gong10Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China; Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, ChinaDepartment of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China; Correspondence to: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.Excessive synthesis of triglycerides and cholesterol accelerates the progression of hepatic steatosis in metabolic-associated fatty liver disease (MAFLD). However, the precise mechanism by which 6-gingerol mitigates hepatic steatosis in MAFLD model mice has yet to be fully understood. The present study observed that 6-gingerol administration exhibited significant protective effects against obesity, insulin resistance, and hepatic steatosis in mice subjected to a high-fat diet (HFD), and mitigated lipid accumulation in HepG2 cells treated with palmitate (PA). Following the hepatic lipidomic analysis, we confirmed that the AMPK-SREBPs signaling pathway as the underlying molecular mechanism by which 6-gingerol inhibited triglyceride and cholesterol biosynthesis, both in vivo and in vitro, through Western blot and immunofluorescence assay. Additionally, the application of an AMPK agonist/inhibitor further validated that 6-gingerol promoted AMPK activation by increasing the phosphorylation level of AMPK in vitro. Notably, the inhibitory effect of 6-gingerol on cholesterol biosynthesis, rather than triglyceride biosynthesis, was significantly diminished after silencing SREBP2 using a lentiviral plasmid shRNA in HepG2 cells. Our study demonstrates that 6-gingerol mitigates hepatic triglyceride and cholesterol biosynthesis to alleviate hepatic steatosis by activating the AMPK-SREBPs signaling pathway, indicating that 6-gingerol may be a potential candidate in the therapy of MAFLD.http://www.sciencedirect.com/science/article/pii/S07533322230185896-GingerolMAFLDTriglyceride biosynthesisCholesterol biosynthesisSREBPs |
| spellingShingle | Qingsong Xia Fuer Lu Yu Chen Jingbin Li Zhaoyi Huang Ke Fang Meilin Hu Yujin Guo Hui Dong Lijun Xu Jing Gong 6-Gingerol regulates triglyceride and cholesterol biosynthesis to improve hepatic steatosis in MAFLD by activating the AMPK-SREBPs signaling pathway Biomedicine & Pharmacotherapy 6-Gingerol MAFLD Triglyceride biosynthesis Cholesterol biosynthesis SREBPs |
| title | 6-Gingerol regulates triglyceride and cholesterol biosynthesis to improve hepatic steatosis in MAFLD by activating the AMPK-SREBPs signaling pathway |
| title_full | 6-Gingerol regulates triglyceride and cholesterol biosynthesis to improve hepatic steatosis in MAFLD by activating the AMPK-SREBPs signaling pathway |
| title_fullStr | 6-Gingerol regulates triglyceride and cholesterol biosynthesis to improve hepatic steatosis in MAFLD by activating the AMPK-SREBPs signaling pathway |
| title_full_unstemmed | 6-Gingerol regulates triglyceride and cholesterol biosynthesis to improve hepatic steatosis in MAFLD by activating the AMPK-SREBPs signaling pathway |
| title_short | 6-Gingerol regulates triglyceride and cholesterol biosynthesis to improve hepatic steatosis in MAFLD by activating the AMPK-SREBPs signaling pathway |
| title_sort | 6 gingerol regulates triglyceride and cholesterol biosynthesis to improve hepatic steatosis in mafld by activating the ampk srebps signaling pathway |
| topic | 6-Gingerol MAFLD Triglyceride biosynthesis Cholesterol biosynthesis SREBPs |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223018589 |
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