CTRP3 attenuates myocardial lipotoxicity via suppression of lipid accumulation, inflammation, apoptosis, and mitochondrial oxidative stress
Myocardial lipotoxicity, a pathophysiological condition characterized by cardiomyocyte damage resulting from dysregulated fatty acid metabolism, plays a pivotal role in cardiovascular disease progression. C1q/tumor necrosis factor-related protein-3 (CTRP3), a novel adipocytokine with pleiotropic met...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2025.1575929/full |
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| author | Qingpeng Wang Jiangyang Chi Chen Wang Yanhong Yuan Rui Tian Yun Yang Xinzhong Chen |
| author_facet | Qingpeng Wang Jiangyang Chi Chen Wang Yanhong Yuan Rui Tian Yun Yang Xinzhong Chen |
| author_sort | Qingpeng Wang |
| collection | DOAJ |
| description | Myocardial lipotoxicity, a pathophysiological condition characterized by cardiomyocyte damage resulting from dysregulated fatty acid metabolism, plays a pivotal role in cardiovascular disease progression. C1q/tumor necrosis factor-related protein-3 (CTRP3), a novel adipocytokine with pleiotropic metabolic regulatory properties, has recently been implicated in lipid homeostasis modulation. Nevertheless, its cardioprotective potential against myocardial lipotoxicity remains poorly understood.ObjectiveA comprehensive approach combining in vivo high-fat diet (HFD) murine models and in vitro palmitic acid-induced cardiomyocyte injury systems was employed.Methodsthis study used animal and cellular experiments to verify the function of CTRP3.ResultsHFD feeding induced significant lipid droplet deposition in cardiomyocytes, concomitant with enhanced inflammatory responses, elevated apoptotic activity, and exacerbated oxidative stress, ultimately leading to cardiac dysfunction. Both cardiac-specific CTRP3 overexpression and exogenous recombinant CTRP3 (rCTRP3) administration demonstrated remarkable cardioprotective effects, manifested through: (1) Significant attenuation of intramyocardial lipid accumulation (p < 0.05) (2) Suppression inflammatory pathways (3) Inhibition of mitochondrial-dependent apoptosis (4) Enhancement of antioxidant defense systems. These coordinated effects substantially ameliorated lipotoxic myocardial damage and improved cardiac functional parameters.ConclusionOur findings reveal that CTRP3 confers robust protection against myocardial lipotoxicity through multi-modal mechanisms involving lipid metabolism regulation, anti-inflammatory actions, apoptosis inhibition, and oxidative stress mitigation, highlighting its therapeutic potential for metabolic cardiomyopathy. |
| format | Article |
| id | doaj-art-3d6e6c530a04435a950579e65fe109a2 |
| institution | DOAJ |
| issn | 2297-055X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj-art-3d6e6c530a04435a950579e65fe109a22025-08-20T02:57:36ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-05-011210.3389/fcvm.2025.15759291575929CTRP3 attenuates myocardial lipotoxicity via suppression of lipid accumulation, inflammation, apoptosis, and mitochondrial oxidative stressQingpeng Wang0Jiangyang Chi1Chen Wang2Yanhong Yuan3Rui Tian4Yun Yang5Xinzhong Chen6Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaMyocardial lipotoxicity, a pathophysiological condition characterized by cardiomyocyte damage resulting from dysregulated fatty acid metabolism, plays a pivotal role in cardiovascular disease progression. C1q/tumor necrosis factor-related protein-3 (CTRP3), a novel adipocytokine with pleiotropic metabolic regulatory properties, has recently been implicated in lipid homeostasis modulation. Nevertheless, its cardioprotective potential against myocardial lipotoxicity remains poorly understood.ObjectiveA comprehensive approach combining in vivo high-fat diet (HFD) murine models and in vitro palmitic acid-induced cardiomyocyte injury systems was employed.Methodsthis study used animal and cellular experiments to verify the function of CTRP3.ResultsHFD feeding induced significant lipid droplet deposition in cardiomyocytes, concomitant with enhanced inflammatory responses, elevated apoptotic activity, and exacerbated oxidative stress, ultimately leading to cardiac dysfunction. Both cardiac-specific CTRP3 overexpression and exogenous recombinant CTRP3 (rCTRP3) administration demonstrated remarkable cardioprotective effects, manifested through: (1) Significant attenuation of intramyocardial lipid accumulation (p < 0.05) (2) Suppression inflammatory pathways (3) Inhibition of mitochondrial-dependent apoptosis (4) Enhancement of antioxidant defense systems. These coordinated effects substantially ameliorated lipotoxic myocardial damage and improved cardiac functional parameters.ConclusionOur findings reveal that CTRP3 confers robust protection against myocardial lipotoxicity through multi-modal mechanisms involving lipid metabolism regulation, anti-inflammatory actions, apoptosis inhibition, and oxidative stress mitigation, highlighting its therapeutic potential for metabolic cardiomyopathy.https://www.frontiersin.org/articles/10.3389/fcvm.2025.1575929/fullCTRP3myocardial lipotoxicitylipid metabolisminflammationoxidative stress |
| spellingShingle | Qingpeng Wang Jiangyang Chi Chen Wang Yanhong Yuan Rui Tian Yun Yang Xinzhong Chen CTRP3 attenuates myocardial lipotoxicity via suppression of lipid accumulation, inflammation, apoptosis, and mitochondrial oxidative stress Frontiers in Cardiovascular Medicine CTRP3 myocardial lipotoxicity lipid metabolism inflammation oxidative stress |
| title | CTRP3 attenuates myocardial lipotoxicity via suppression of lipid accumulation, inflammation, apoptosis, and mitochondrial oxidative stress |
| title_full | CTRP3 attenuates myocardial lipotoxicity via suppression of lipid accumulation, inflammation, apoptosis, and mitochondrial oxidative stress |
| title_fullStr | CTRP3 attenuates myocardial lipotoxicity via suppression of lipid accumulation, inflammation, apoptosis, and mitochondrial oxidative stress |
| title_full_unstemmed | CTRP3 attenuates myocardial lipotoxicity via suppression of lipid accumulation, inflammation, apoptosis, and mitochondrial oxidative stress |
| title_short | CTRP3 attenuates myocardial lipotoxicity via suppression of lipid accumulation, inflammation, apoptosis, and mitochondrial oxidative stress |
| title_sort | ctrp3 attenuates myocardial lipotoxicity via suppression of lipid accumulation inflammation apoptosis and mitochondrial oxidative stress |
| topic | CTRP3 myocardial lipotoxicity lipid metabolism inflammation oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2025.1575929/full |
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