Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation
Abstract Background Previous studies demonstrated impaired lipid metabolism and augmented aerobic glycolysis in AF. The authors aimed to investigate whether the use of metformin, an AMPK activator, could reverse this metabolic remodeling in chronic AF and to explore the underlying mechanisms. Method...
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | BMC Cardiovascular Disorders |
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| Online Access: | https://doi.org/10.1186/s12872-020-01359-7 |
| _version_ | 1818452865693253632 |
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| author | Yaozhong Liu Fan Bai Na Liu Baojian Zhang Fen Qin Tao Tu Biao Li Jiayi Li Yingxu Ma Feifan Ouyang Qiming Liu |
| author_facet | Yaozhong Liu Fan Bai Na Liu Baojian Zhang Fen Qin Tao Tu Biao Li Jiayi Li Yingxu Ma Feifan Ouyang Qiming Liu |
| author_sort | Yaozhong Liu |
| collection | DOAJ |
| description | Abstract Background Previous studies demonstrated impaired lipid metabolism and augmented aerobic glycolysis in AF. The authors aimed to investigate whether the use of metformin, an AMPK activator, could reverse this metabolic remodeling in chronic AF and to explore the underlying mechanisms. Methods We conducted chronic AF animal models with 18 beagle dogs and divided them into SR (pacemaker implanted without pacing), AF (pacemaker implanted with sustained pacing at a frequency of 400 beats/min for 6 weeks), and metformin+AF group (daily oral administration of metformin was initiated 1 week before surgery and continued throughout the study period). After electrophysiological measurements, the left atrial appendage tissue samples were taken from the beating heart for further analysis. Protein expression, histological analysis, and biochemical measurements were conducted. Results The AF groups showed decreased expression of FAT/CD36, CPT-1, VLCAD, increased concentration of free fatty acid and triglyceride, and increased lipid deposition. The activation of AMPK/PGC-1α/PPARα pathway was decreased. The key factors of the Warburg effect, including HIF-1α, GLUT-1, PDK1, HK, and LDH, increased in AF group compared to SR group. The expression of PDH decreased significantly, accompanied by increased atrial lactate production. The extent of fibrosis increased significantly in the left atrial appendage of AF group. dERP, ∑WOV, and AF inducibility increased while ERP decreased in AF group compared to SR group. The use of metformin attenuated all these changes effectively. Conclusions Metformin improves lipid metabolism and reverses the Warburg effect in chronic AF via AMPK activation. It attenuates atrial electrical and structural remodeling. |
| first_indexed | 2024-12-14T21:29:53Z |
| format | Article |
| id | doaj.art-be41e36136ce4eea8f543d9ea141a333 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-12-14T21:29:53Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-be41e36136ce4eea8f543d9ea141a3332022-12-21T22:46:43ZengBMCBMC Cardiovascular Disorders1471-22612020-02-012011910.1186/s12872-020-01359-7Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillationYaozhong Liu0Fan Bai1Na Liu2Baojian Zhang3Fen Qin4Tao Tu5Biao Li6Jiayi Li7Yingxu Ma8Feifan Ouyang9Qiming Liu10Dept. of Cardiovascular Medicine/Cardiac Catheterization Lab. Second Xiangya Hospital, Central South UniversityDept. of Cardiovascular Medicine/Cardiac Catheterization Lab. Second Xiangya Hospital, Central South UniversityDept. of Cardiovascular Medicine/Cardiac Catheterization Lab. Second Xiangya Hospital, Central South UniversityDept. of Cardiovascular Medicine/Cardiac Catheterization Lab. Second Xiangya Hospital, Central South UniversityDept. of Cardiovascular Medicine/Cardiac Catheterization Lab. Second Xiangya Hospital, Central South UniversityDept. of Cardiovascular Medicine/Cardiac Catheterization Lab. Second Xiangya Hospital, Central South UniversityDept. of Cardiovascular Medicine/Cardiac Catheterization Lab. Second Xiangya Hospital, Central South UniversityDept. of Cardiovascular Medicine/Cardiac Catheterization Lab. Second Xiangya Hospital, Central South UniversityDept. of Cardiovascular Medicine/Cardiac Catheterization Lab. Second Xiangya Hospital, Central South UniversityDepartment of Cardiology, Asklepios-Klinik St GeorgDept. of Cardiovascular Medicine/Cardiac Catheterization Lab. Second Xiangya Hospital, Central South UniversityAbstract Background Previous studies demonstrated impaired lipid metabolism and augmented aerobic glycolysis in AF. The authors aimed to investigate whether the use of metformin, an AMPK activator, could reverse this metabolic remodeling in chronic AF and to explore the underlying mechanisms. Methods We conducted chronic AF animal models with 18 beagle dogs and divided them into SR (pacemaker implanted without pacing), AF (pacemaker implanted with sustained pacing at a frequency of 400 beats/min for 6 weeks), and metformin+AF group (daily oral administration of metformin was initiated 1 week before surgery and continued throughout the study period). After electrophysiological measurements, the left atrial appendage tissue samples were taken from the beating heart for further analysis. Protein expression, histological analysis, and biochemical measurements were conducted. Results The AF groups showed decreased expression of FAT/CD36, CPT-1, VLCAD, increased concentration of free fatty acid and triglyceride, and increased lipid deposition. The activation of AMPK/PGC-1α/PPARα pathway was decreased. The key factors of the Warburg effect, including HIF-1α, GLUT-1, PDK1, HK, and LDH, increased in AF group compared to SR group. The expression of PDH decreased significantly, accompanied by increased atrial lactate production. The extent of fibrosis increased significantly in the left atrial appendage of AF group. dERP, ∑WOV, and AF inducibility increased while ERP decreased in AF group compared to SR group. The use of metformin attenuated all these changes effectively. Conclusions Metformin improves lipid metabolism and reverses the Warburg effect in chronic AF via AMPK activation. It attenuates atrial electrical and structural remodeling.https://doi.org/10.1186/s12872-020-01359-7Atrial fibrillationMetabolismMetforminWarburg effectAMPK |
| spellingShingle | Yaozhong Liu Fan Bai Na Liu Baojian Zhang Fen Qin Tao Tu Biao Li Jiayi Li Yingxu Ma Feifan Ouyang Qiming Liu Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation BMC Cardiovascular Disorders Atrial fibrillation Metabolism Metformin Warburg effect AMPK |
| title | Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation |
| title_full | Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation |
| title_fullStr | Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation |
| title_full_unstemmed | Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation |
| title_short | Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation |
| title_sort | metformin improves lipid metabolism and reverses the warburg effect in a canine model of chronic atrial fibrillation |
| topic | Atrial fibrillation Metabolism Metformin Warburg effect AMPK |
| url | https://doi.org/10.1186/s12872-020-01359-7 |
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