心衰发生发展过程中心肌对脂肪酸的利用降低并伴有线粒体损伤，新近发现通过膳食（高脂饮食）增加心肌对脂肪酸的利用对心衰具有改善作用。我们研究发现脂肪酸发挥心肌保护作用的机制与其改善线粒体质量有关。心衰时心肌对脂肪酸的利用降低致线粒体损伤，但损伤线粒体的清除（线粒体自噬）被抑制；增加心肌脂摄入显著改善线粒体质量，并促进线粒体自噬；离体实验结果表明脂肪酸能够促进ULK1向线粒体转位并增加线粒体自噬：提示脂肪酸可能通过ULK1促进线粒体自噬发挥心衰改善作用。本研究拟阐明脂肪酸促进心肌线粒体自噬的机制及其在心衰发生发展中的作用和在心衰防治中的应用：明确不同脂肪酸（包含酮体）及其代谢产物对心肌线粒体自噬的影响；阐明脂肪酸调控线粒体自噬的分子机制；明确脂肪酸调控线粒体自噬在心衰发生发展中的作用及探讨如何通过膳食干预心肌脂代谢改善心衰。本研究有望揭示脂肪酸改善心衰的机制，为从膳食角度防治心衰提供新线索。

Heart failure is characterized by reduced fatty acids (FA) utilization associated with mitochondrial dysfunction. Recent studies have shown that enhancing FA utilization through treatment with high fat diet exerts cardioprotection against heart failure. We recently found that FA exerts cardioprotection through improvement of mitochondrial quality in the failing heart. Heart failure was associated with mitochondrial dysfunction which was resulted from a decrease of cardiac FA utilization. However, mitophagy, a process for clearance of damaged mitochondria, was suppressed. Enhancing FA utilization improved mitochondrial quality and promoted mitophagy. In addition, FA increased mitophagy and ULK1 translocation into mitochondria in a dose-dependent manner in vitro. These results suggested that FA may protect the failing heart through ULK1-mediated mitophagy. Thus, our aim is to investigate the effects of FA on cardiac mitophagy and its underlying mechanisms and application in cardioprotection against heart failure. This study was designed to 1) examine the effects of different types of FA (including ketone body) and its metabolic products on cardiac mitophagy; 2) explore the underlying mechanisms of the regulation of mitophagy by FA; 3) examine the role of this regulation in the development of heart failure and search for new strategy for intervention of heart failure through diet. This study will elucidate a novel role of FA in the regulation of mitochondrial quality and its role in the development of heart failure, providing new clues for the intervention of heart failure through diet.