Astragaloside IV alleviates heart failure via activating PPARα to switch glycolysis to fatty acid β-oxidation

作者：Zhiwei Dong, Pei Zhao, Ming Xu, Chen Zhang, Wei Guo, Huihua Chen, Jing Tian, Hongchang Wei, Rong Lü, Tongtong Cao · 发表于：Scientific Reports · 年份：2017 · DOI：10.1038/s41598-017-02360-5 · 被引用次数：103 · 研究领域：Cardiovascular Function and Risk Factors、Mitochondrial Function and Pathology、Adipose Tissue and Metabolism

Abstract In heart failure (HF), energy metabolism pathway in cardiac muscle changes from fatty acid β-oxidation to glycolysis. However, the exact mechanism is unknown. Sarcoendoplasmic reticulum Ca 2+ α ATPase (SERCA) expression is downregulated and mitochondrial function is reduced in HF, perhaps partly due to a substantially reduced energy supply for excitation–contraction coupling resulting from a lower fatty acid β-oxidation rate. We investigated whether Astragaloside IV can activate peroxisome proliferator-activated receptor alpha (PPARα) to stimulate fatty acid β-oxidation and increase cardiac energy production, improving mitochondrial function and the efficiency of SERCA in HF. In pressure overload-induced HF mice and isolated hypertrophic myocardial cells, fatty acid β-oxidation and heart function were substantially strengthened following Astragaloside IV treatment, as demonstrated by the increased expression of PPARα and SERCA2a. In vitro , Astragaloside IV regulated energy metabolism by increasing ATP production and enhancing mitochondrial function, attributable to increased oxygen consumption and slightly increased mitochondrial Ca 2+ uptake. In HF, Astragaloside IV switched glycolysis to fatty acid β-oxidation, as confirmed by reduced anaerobic glycolysis and an increased oxygen consumption ratio. These results suggest that Astragaloside IV can stimulate fatty acid β-oxidation and improve mitochondrial function, which may present a novel cardioprotective treatment...