Nature子刊：饮食方式或可调节心力衰竭小鼠的病症 | 热心肠日报

线粒体丙酮酸载体缺陷小鼠中心力衰竭的营养调节

10.1038/s42255-020-00296-1

10-26, Article

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The myocardium is metabolically flexible; however, impaired flexibility is associated with cardiac dysfunction in conditions including diabetes and heart failure. The mitochondrial pyruvate carrier (MPC) complex, composed of MPC1 and MPC2, is required for pyruvate import into the mitochondria. Here we show that MPC1 and MPC2 expression is downregulated in failing human and mouse hearts. Mice with cardiac-specific deletion of Mpc2 (CS-MPC2−/−) exhibited normal cardiac size and function at 6 weeks old, but progressively developed cardiac dilation and contractile dysfunction, which was completely reversed by a high-fat, low-carbohydrate ketogenic diet. Diets with higher fat content, but enough carbohydrate to limit ketosis, also improved heart failure, while direct ketone body provisioning provided only minor improvements in cardiac remodelling in CS-MPC2−/− mice. An acute fast also improved cardiac remodelling. Together, our results reveal a critical role for mitochondrial pyruvate use in cardiac function, and highlight the potential of dietary interventions to enhance cardiac fat metabolism to prevent or reverse cardiac dysfunction and remodelling in the setting of MPC deficiency.

First Authors:
Kyle S McCommis

Correspondence Authors:
Kyle S McCommis

All Authors:
Kyle S McCommis,Attila Kovacs,Carla J Weinheimer,Trevor M Shew,Timothy R Koves,Olga R Ilkayeva,Dakota R Kamm,Kelly D Pyles,M Todd King,Richard L Veech,Brian J DeBosch,Deborah M Muoio,Richard W Gross,Brian N Finck