Rationale: Pregnancy profoundly alters maternal physiology. The heart hypertrophies during pregnancy, but its metabolic adaptations, are not well understood.

Objective: To determine the mechanisms underlying cardiac substrate use during pregnancy.

Methods and Results: We use here ¹³C glucose, ¹³C lactate, and ¹³C fatty acid tracing analyses to show that hearts in late pregnant mice increase fatty acid uptake and oxidation into the tricarboxylic acid cycle, while reducing glucose and lactate oxidation. Mitochondrial quantity, morphology, and function do not seem altered. Insulin signaling seems intact, and the abundance and localization of the major fatty acid and glucose transporters, CD36 (cluster of differentiation 36) and GLUT4 (glucose transporter type 4), are also unchanged. Rather, we find that the pregnancy hormone progesterone induces PDK4 (pyruvate dehydrogenase kinase 4) in cardiomyocytes and that elevated PDK4 levels in late pregnancy lead to inhibition of PDH (pyruvate dehydrogenase) and pyruvate flux into the tricarboxylic acid cycle. Blocking PDK4 reverses the metabolic changes seen in hearts in late pregnancy.

Conclusions: Taken together, these data indicate that the hormonal environment of late pregnancy promotes metabolic remodeling in the heart at the level of PDH, rather than at the level of insulin signaling.

理由：怀孕会极大地改变孕产妇的生理状况。怀孕期间心脏肥大，但其代谢适应性尚不十分清楚。

目的：确定怀孕期间心脏底物使用的潜在机制。

方法和结果：我们在这里使用¹³ C葡萄糖， ¹³ C乳酸和¹³ CC脂肪酸示踪分析显示，妊娠晚期小鼠的心脏增加了脂肪酸的吸收和三羧酸循环中的氧化，同时减少了葡萄糖和乳酸的氧化。线粒体的数量，形态和功能似乎没有改变。胰岛素信号似乎完整无缺，主要脂肪酸和葡萄糖转运蛋白CD36（分化簇36）和GLUT4（葡萄糖转运蛋白4型）的丰度和定位也未改变。相反，我们发现妊娠激素黄体酮在心肌细胞中诱导了PDK4（丙酮酸脱氢酶激酶4），并且妊娠后期的PDK4水平升高导致PDH（丙酮酸脱氢酶）的抑制和丙酮酸通入三羧酸循环。阻断PDK4可逆转妊娠晚期心脏中的新陈代谢变化。

结论：综上所述，这些数据表明妊娠后期的激素环境在PDH水平而非胰岛素信号水平促进了心脏的代谢重塑。