Exercise improves high-fat diet-induced lipid metabolic and cardiac dysfunction via AMPK-PGC-1α/dLipin

High-fat diet (HFD)-induced lipid metabolism abnormalities and cardiac dysfunction are important risk factors for cardiovascular disease. Although exercise can improve lipid metabolism abnormalities, its molecular mechanisms remain unclear. This study used Drosophila as a model to investigate the regulatory mechanisms of exercise on HFD-induced lipid metabolism abnormalities and cardiac dysfunction. Results showed that HFD caused lipid accumulation, impaired cardiac contractility, and arrhythmia in fly, accompanied by upregulation of dLipin expression and suppression of the AMPK-PGC-1α signaling pathway in cardiomyocytes. Exercise intervention activated the AMPK-PGC-1α axis to transcriptionally inhibit dLipin, thereby improving HFD-induced lipid metabolism abnormalities and cardiac dysfunction. Knockdown experiments confirmed that dLipin knockdown in cardiomyocytes protected against HFD-induced lipid metabolic abnormalities and cardiac dysfunction, while PGC-1α knockdown blocked the inhibitory effect of exercise on dLipin and its cardiac protective effects. This study reveals that exercise improves HFD-induced lipid metabolic abnormalities and cardiac dysfunction through the AMPK-PGC-1α/dLipin pathway, providing a new strategy for targeted treatment of obesity-related cardiovascular diseases.