Activating cardiac E2F1 induces up-regulation of pyruvate dehydrogenase kinase 4 in mice on a short term of high fat feeding

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• 作者：Liyan Zhang ; Jun Mori ; Cory Wagg ; Gary D. Lopaschuk ; ^{gary.lopaschuk@ualberta.ca}
• 关键词：HFD ; high fat diet ; LFD ; low fat diet ; PDC ; pyruvate dehydrogenase complex ; PDK4 ; pyruvate dehydrogenase kinase 4 ; Rb ; retinoblastoma ; PPAR¦Á ; peroxisome proliferator-activated receptor ; PGC-1¦Á ; peroxisome proliferator-activated receptor gamma coactivato
• 刊名：FEBS Letters
• 出版年：2012
• 出版时间：5 April, 2012
• 年：2012
• 卷：586
• 期：7
• 页码：996-1003
• 全文大小：954 K

文摘

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 10 days. 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.