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Activating cardiac E2F1 induces up‐regulation of pyruvate dehydrogenase kinase 4 in mice on a short term of high fat feeding
Author(s) -
Zhang Liyan,
Mori Jun,
Wagg Cory,
Lopaschuk Gary D.
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.02.027
Subject(s) - pdk4 , pyruvate dehydrogenase kinase , pyruvate dehydrogenase complex , e2f1 , cyclin dependent kinase 5 , endocrinology , transcription factor , biology , medicine , kinase , chemistry , microbiology and biotechnology , biochemistry , protein kinase a , cyclin dependent kinase 2 , enzyme , gene
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.