Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism
Abstract Background Increased circulating uric acid (UA) concentration may disrupt cardiac function in heart failure patients, but the specific mechanism remains unclear. Here, we postulate that hyperuremia induces sterol regulatory element binding protein 1 (SREBP1), which in turn activate hepatic...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04050-5 |
| _version_ | 1827982902706569216 |
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| author | Bowen Lou Haoyu Wu Hannes Ott Katrin Bennewitz Chen Wang Gernot Poschet Hui Liu Zuyi Yuan Jens Kroll Jianqing She |
| author_facet | Bowen Lou Haoyu Wu Hannes Ott Katrin Bennewitz Chen Wang Gernot Poschet Hui Liu Zuyi Yuan Jens Kroll Jianqing She |
| author_sort | Bowen Lou |
| collection | DOAJ |
| description | Abstract Background Increased circulating uric acid (UA) concentration may disrupt cardiac function in heart failure patients, but the specific mechanism remains unclear. Here, we postulate that hyperuremia induces sterol regulatory element binding protein 1 (SREBP1), which in turn activate hepatic fatty acid biosynthesis response, leading to cardiac dysfunction. Methods and results Increased circulating uric acid was observed in heart failure patients and inversely correlated to cardiac function. Besides, uric acid correlated to circulating lipids profile based on metabolomics in heart failure patients. Using cultured human hepatoellular carcinomas (HepG2) and Tg(myl7:egfp) zebrafish, we demonstrated that UA regulated fatty acid synthase (FASN) via SREBP1 signaling pathway, leading to FFA accumulation and impaired energy metabolism, which could be rescued via SREBP1 knockdown. In ISO treated zebrafish, UA aggravated heart failure via increased cardiovascular cavity size, decreased heart beats, pericardial edema and long-stretched heart deformation. Conclusions Our findings suggest that UA-SREBP1-FASN signaling exacerbates cardiac dysfunction during FFA accumulation. Identification of this mechanism may help in treatment and prevention of heart failure. |
| first_indexed | 2024-04-09T22:40:25Z |
| format | Article |
| id | doaj.art-57b81c6c80614279a17b07c0f715d412 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-09T22:40:25Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-57b81c6c80614279a17b07c0f715d4122023-03-22T12:14:01ZengBMCJournal of Translational Medicine1479-58762023-03-0121111510.1186/s12967-023-04050-5Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolismBowen Lou0Haoyu Wu1Hannes Ott2Katrin Bennewitz3Chen Wang4Gernot Poschet5Hui Liu6Zuyi Yuan7Jens Kroll8Jianqing She9Cardiovascular Department, The First Affiliated Hospital of Xi’an Jiaotong UniversityCardiovascular Department, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg UniversityDepartment of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg UniversityCardiovascular Department, The First Affiliated Hospital of Xi’an Jiaotong UniversityMetabolomics Core Technology Platform, Centre for Organismal Studies, Heidelberg UniversityFirst Affiliated Hospital of Xi’an Jiaotong UniversityCardiovascular Department, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg UniversityCardiovascular Department, The First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Background Increased circulating uric acid (UA) concentration may disrupt cardiac function in heart failure patients, but the specific mechanism remains unclear. Here, we postulate that hyperuremia induces sterol regulatory element binding protein 1 (SREBP1), which in turn activate hepatic fatty acid biosynthesis response, leading to cardiac dysfunction. Methods and results Increased circulating uric acid was observed in heart failure patients and inversely correlated to cardiac function. Besides, uric acid correlated to circulating lipids profile based on metabolomics in heart failure patients. Using cultured human hepatoellular carcinomas (HepG2) and Tg(myl7:egfp) zebrafish, we demonstrated that UA regulated fatty acid synthase (FASN) via SREBP1 signaling pathway, leading to FFA accumulation and impaired energy metabolism, which could be rescued via SREBP1 knockdown. In ISO treated zebrafish, UA aggravated heart failure via increased cardiovascular cavity size, decreased heart beats, pericardial edema and long-stretched heart deformation. Conclusions Our findings suggest that UA-SREBP1-FASN signaling exacerbates cardiac dysfunction during FFA accumulation. Identification of this mechanism may help in treatment and prevention of heart failure.https://doi.org/10.1186/s12967-023-04050-5Uric acidFatty acidSterol regulatory element binding proteins 1Heart failure |
| spellingShingle | Bowen Lou Haoyu Wu Hannes Ott Katrin Bennewitz Chen Wang Gernot Poschet Hui Liu Zuyi Yuan Jens Kroll Jianqing She Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism Journal of Translational Medicine Uric acid Fatty acid Sterol regulatory element binding proteins 1 Heart failure |
| title | Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism |
| title_full | Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism |
| title_fullStr | Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism |
| title_full_unstemmed | Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism |
| title_short | Increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism |
| title_sort | increased circulating uric acid aggravates heart failure via impaired fatty acid metabolism |
| topic | Uric acid Fatty acid Sterol regulatory element binding proteins 1 Heart failure |
| url | https://doi.org/10.1186/s12967-023-04050-5 |
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