The ketogenic diet does not improve cardiac function and blunts glucose oxidation in ischaemic heart failure

作者：Kim L. Ho, Qutuba G. Karwi, Faqi Wang, Cory S. Wagg, Liyan Zhang, Sai Panidarapu, Brandon Chen, Simran Pherwani, Amanda A. Greenwell, Gavin Y. Oudit, John R. Ussher, Gary D. Lopaschuk · 发表于：Cardiovascular Research · 年份：2024 · DOI：10.1093/cvr/cvae092 · 被引用次数：22 · 研究领域：Diet and metabolism studies、Cardiovascular Function and Risk Factors、Fatty Acid Research and Health

AIMS: Cardiac energy metabolism is perturbed in ischaemic heart failure and is characterized by a shift from mitochondrial oxidative metabolism to glycolysis. Notably, the failing heart relies more on ketones for energy than a healthy heart, an adaptive mechanism that improves the energy-starved status of the failing heart. However, whether this can be implemented therapeutically remains unknown. Therefore, our aim was to determine if increasing ketone delivery to the heart via a ketogenic diet can improve the outcomes of heart failure. METHODS AND RESULTS: C57BL/6J male mice underwent either a sham surgery or permanent left anterior descending coronary artery ligation surgery to induce heart failure. After 2 weeks, mice were then treated with either a control diet or a ketogenic diet for 3 weeks. Transthoracic echocardiography was then carried out to assess in vivo cardiac function and structure. Finally, isolated working hearts from these mice were perfused with appropriately 3H or 14C labelled glucose (5 mM), palmitate (0.8 mM), and β-hydroxybutyrate (β-OHB) (0.6 mM) to assess mitochondrial oxidative metabolism and glycolysis. Mice with heart failure exhibited a 56% drop in ejection fraction, which was not improved with a ketogenic diet feeding. Interestingly, mice fed a ketogenic diet had marked decreases in cardiac glucose oxidation rates. Despite increasing blood ketone levels, cardiac ketone oxidation rates did not increase, probably due to a decreased expression of ke...