Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada.
FEBS Lett. 2012 Apr 5;586(7):996-1003. doi: 10.1016/j.febslet.2012.02.027. Epub 2012 Mar 3.
A high fat diet (HFD) induces substantial cardiac metabolic alteration(s), but the initiating molecular events remain unclear. We assessed the early cardiac energy metabolic changes in C57/BJ mice fed a HFD for 10days. Carbohydrate oxidation was markedly decreased in mice on a HFD, in which up-regulation of pyruvate dehydrogenase kinase 4 (PDK4) was evident. Concurrently, E2F1, a transcription factor controlling PDK4 expression, was activated, as was cyclin D1, an upstream-molecule of E2F1, and eukaryotic initiation factor 4E (eIF4E), a modulator of cyclinD1 translation. Hence, HFD may initiate early cardiac metabolic alterations through the eIF4E/cyclin D1/E2F1/PDK4 axis.
高脂肪饮食（HFD）可引起显著的心脏代谢改变，但起始的分子事件尚不清楚。我们评估了饲喂 HFD10 天的 C57/BJ 小鼠的早期心脏能量代谢变化。HFD 喂养的小鼠的碳水化合物氧化明显减少，其中丙酮酸脱氢酶激酶 4（PDK4）的上调是明显的。同时，转录因子 E2F1 及其上游分子细胞周期蛋白 D1 和真核起始因子 4E（eIF4E）的激活，均可调控 PDK4 的表达，eIF4E 是细胞周期蛋白 D1 翻译的调节剂。因此，HFD 可能通过 eIF4E/细胞周期蛋白 D1/E2F1/PDK4 轴引发早期心脏代谢改变。
