Exerkine β-aminoisobutyric acid protects against atrial structural remodeling and atrial fibrillation in obesity via activating AMPK signaling and improving insulin sensitivity

作者：Xinghua Qin, Peng Liu, Lingyan Jin, Ke Zhu, Yuanqing Yang, Zuoxu Hou, Huiliang Zhang, Qiangsun Zheng · 发表于：Biomedicine & Pharmacotherapy · 年份：2024 · DOI：10.1016/j.biopha.2024.116137 · 被引用次数：16 · 研究领域：Cardiovascular Function and Risk Factors、Atrial Fibrillation Management and Outcomes、Cardiovascular Disease and Adiposity

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 atten...