Exerkine β-aminoisobutyric acid protects against atrial structural remodeling and atrial fibrillation in obesity via activating AMPK signaling and improving insulin sensitivity
Moderate exercise decreases the risk for atrial fibrillation (AF), an effect which is probably mediated via exercise-stimulated release of exerkines. β-Aminoisobutyric acid (BAIBA), a novel exerkine, has been reported to provide protective benefits against many cardiovascular diseases, yet its role...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-02-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332224000180 |
| _version_ | 1797324328393506816 |
|---|---|
| author | Xinghua Qin Peng Liu Lingyan Jin Ke Zhu Yuanqing Yang Zuoxu Hou Huiliang Zhang Qiangsun Zheng |
| author_facet | Xinghua Qin Peng Liu Lingyan Jin Ke Zhu Yuanqing Yang Zuoxu Hou Huiliang Zhang Qiangsun Zheng |
| author_sort | Xinghua Qin |
| collection | DOAJ |
| description | Moderate exercise decreases the risk for atrial fibrillation (AF), an effect which is probably mediated via exercise-stimulated release of exerkines. β-Aminoisobutyric acid (BAIBA), a novel exerkine, has been reported to provide protective benefits against many cardiovascular diseases, yet its role in AF remains elusive. Herein, using a mouse model of obesity-related AF through high-fat diet (HFD) feeding, we found that 12-week drinking administration of BAIBA (170 mg/kg/day) decreased AF susceptibility in obese mice. Atrial remodeling assessment showed that BAIBA attenuated obesity-induced atrial hypertrophy and interstitial fibrosis, thereby ablating the substrate for AF. Of note, to our knowledge, this is the first report of the direct association of BAIBA and hypertrophy. BAIBA has been reported to be a key regulator of glucose and lipid metabolism, and we found that BAIBA alleviated insulin resistance in obese mice. Transcriptional analysis of metabolism-related genes showed that BAIBA increased the transcription of fatty acids metabolism-related genes in the atria of lean mice but not in that of obese mice. Mechanistic investigation showed that BAIBA stimulated AMP-activated protein kinase (AMPK) signaling in the atria of obese mice and palmitic acid (PA)-treated neonatal rat cardiomyocytes (NRCM), whereas inhibition of AMPK via Compound C attenuated BAIBA-conferred cardioprotection against hypertrophy and insulin resistance in PA-treated NRCM. Collectively, BAIBA attenuates AF susceptibility in obese mice via activated AMPK signaling and resultant improvement of insulin sensitivity, thereby providing perspectives on the potential therapeutic role of BAIBA in AF treatment. |
| first_indexed | 2024-03-08T05:55:32Z |
| format | Article |
| id | doaj.art-4b3d96a8c54c41b1b63490c56ca3fcb4 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-08T05:55:32Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-4b3d96a8c54c41b1b63490c56ca3fcb42024-02-05T04:31:14ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-02-01171116137Exerkine β-aminoisobutyric acid protects against atrial structural remodeling and atrial fibrillation in obesity via activating AMPK signaling and improving insulin sensitivityXinghua Qin0Peng Liu1Lingyan Jin2Ke Zhu3Yuanqing Yang4Zuoxu Hou5Huiliang Zhang6Qiangsun Zheng7Xi'an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China; Correspondence to: School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, ChinaDepartment of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, ChinaXi'an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, ChinaXi'an Key Laboratory of Special Medicine and Health Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, ChinaDepartment of Orthopedics, Shenzhen Hospital of Southern Medical University, Shenzhen 518000, ChinaDepartment of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China; Corresponding author.Moderate exercise decreases the risk for atrial fibrillation (AF), an effect which is probably mediated via exercise-stimulated release of exerkines. β-Aminoisobutyric acid (BAIBA), a novel exerkine, has been reported to provide protective benefits against many cardiovascular diseases, yet its role in AF remains elusive. Herein, using a mouse model of obesity-related AF through high-fat diet (HFD) feeding, we found that 12-week drinking administration of BAIBA (170 mg/kg/day) decreased AF susceptibility in obese mice. Atrial remodeling assessment showed that BAIBA attenuated obesity-induced atrial hypertrophy and interstitial fibrosis, thereby ablating the substrate for AF. Of note, to our knowledge, this is the first report of the direct association of BAIBA and hypertrophy. BAIBA has been reported to be a key regulator of glucose and lipid metabolism, and we found that BAIBA alleviated insulin resistance in obese mice. Transcriptional analysis of metabolism-related genes showed that BAIBA increased the transcription of fatty acids metabolism-related genes in the atria of lean mice but not in that of obese mice. Mechanistic investigation showed that BAIBA stimulated AMP-activated protein kinase (AMPK) signaling in the atria of obese mice and palmitic acid (PA)-treated neonatal rat cardiomyocytes (NRCM), whereas inhibition of AMPK via Compound C attenuated BAIBA-conferred cardioprotection against hypertrophy and insulin resistance in PA-treated NRCM. Collectively, BAIBA attenuates AF susceptibility in obese mice via activated AMPK signaling and resultant improvement of insulin sensitivity, thereby providing perspectives on the potential therapeutic role of BAIBA in AF treatment.http://www.sciencedirect.com/science/article/pii/S0753332224000180Atrial fibrillationβ-Aminoisobutyric AcidMetabolic flexibilityInsulin resistanceAMP-activated protein kinase |
| spellingShingle | Xinghua Qin Peng Liu Lingyan Jin Ke Zhu Yuanqing Yang Zuoxu Hou Huiliang Zhang Qiangsun Zheng Exerkine β-aminoisobutyric acid protects against atrial structural remodeling and atrial fibrillation in obesity via activating AMPK signaling and improving insulin sensitivity Biomedicine & Pharmacotherapy Atrial fibrillation β-Aminoisobutyric Acid Metabolic flexibility Insulin resistance AMP-activated protein kinase |
| title | Exerkine β-aminoisobutyric acid protects against atrial structural remodeling and atrial fibrillation in obesity via activating AMPK signaling and improving insulin sensitivity |
| title_full | Exerkine β-aminoisobutyric acid protects against atrial structural remodeling and atrial fibrillation in obesity via activating AMPK signaling and improving insulin sensitivity |
| title_fullStr | Exerkine β-aminoisobutyric acid protects against atrial structural remodeling and atrial fibrillation in obesity via activating AMPK signaling and improving insulin sensitivity |
| title_full_unstemmed | Exerkine β-aminoisobutyric acid protects against atrial structural remodeling and atrial fibrillation in obesity via activating AMPK signaling and improving insulin sensitivity |
| title_short | Exerkine β-aminoisobutyric acid protects against atrial structural remodeling and atrial fibrillation in obesity via activating AMPK signaling and improving insulin sensitivity |
| title_sort | exerkine β aminoisobutyric acid protects against atrial structural remodeling and atrial fibrillation in obesity via activating ampk signaling and improving insulin sensitivity |
| topic | Atrial fibrillation β-Aminoisobutyric Acid Metabolic flexibility Insulin resistance AMP-activated protein kinase |
| url | http://www.sciencedirect.com/science/article/pii/S0753332224000180 |
| work_keys_str_mv | AT xinghuaqin exerkinebaminoisobutyricacidprotectsagainstatrialstructuralremodelingandatrialfibrillationinobesityviaactivatingampksignalingandimprovinginsulinsensitivity AT pengliu exerkinebaminoisobutyricacidprotectsagainstatrialstructuralremodelingandatrialfibrillationinobesityviaactivatingampksignalingandimprovinginsulinsensitivity AT lingyanjin exerkinebaminoisobutyricacidprotectsagainstatrialstructuralremodelingandatrialfibrillationinobesityviaactivatingampksignalingandimprovinginsulinsensitivity AT kezhu exerkinebaminoisobutyricacidprotectsagainstatrialstructuralremodelingandatrialfibrillationinobesityviaactivatingampksignalingandimprovinginsulinsensitivity AT yuanqingyang exerkinebaminoisobutyricacidprotectsagainstatrialstructuralremodelingandatrialfibrillationinobesityviaactivatingampksignalingandimprovinginsulinsensitivity AT zuoxuhou exerkinebaminoisobutyricacidprotectsagainstatrialstructuralremodelingandatrialfibrillationinobesityviaactivatingampksignalingandimprovinginsulinsensitivity AT huiliangzhang exerkinebaminoisobutyricacidprotectsagainstatrialstructuralremodelingandatrialfibrillationinobesityviaactivatingampksignalingandimprovinginsulinsensitivity AT qiangsunzheng exerkinebaminoisobutyricacidprotectsagainstatrialstructuralremodelingandatrialfibrillationinobesityviaactivatingampksignalingandimprovinginsulinsensitivity |