• 心脏衰竭的人和小鼠中,线粒体丙酮酸载体(MPC)1和2的表达下调;
  • 心脏特异性缺失Mpc2(CS-MPC2-/-)的小鼠丙酮酸代谢改变,TCA循环缺陷;
  • CS-MPC2-/-小鼠在6周龄时心脏大小和功能表现正常,但逐渐发展为心力衰竭,高脂肪、低碳水的生酮饮食可完全逆转其心力衰竭;
  • 高脂肪和足量碳水化合物的饮食可改善心力衰竭,而直接补充酮体只对CS-MPC2-/-小鼠的心脏重构有轻微改善;
  • 急性禁食改善心脏重塑,与脂肪氧化增加有关。
心肌的代谢具有灵活性,但在糖尿病和心力衰竭等情况下,代谢灵活性受损,导致心脏功能不全。MPC1和MPC2组成线粒体丙酮酸载体(MPC)复合体,是丙酮酸转运到线粒体所必需的。Nature Metabolism近期发表的文章,发现心脏特异性缺失MPC2导致小鼠丙酮酸代谢改变,发展成心力衰竭。高脂肪低碳水的生酮饮食、高脂肪高碳水的饮食以及急性禁食都有利于改善心力衰竭。这表明线粒体丙酮酸代谢在心脏功能中的重要作用,并证明饮食干预可增强MPC缺陷小鼠的心脏脂肪代谢,预防或逆转心脏功能不全,并有助于重塑心脏。

Nutritional modulation of heart failure in mitochondrial pyruvate carrier–deficient mice



2020-10-26, Article

Abstract & Authors:展开

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

Nature Metabolism期刊

Ketone bodies for the starving heart