Unbound MEDLINE

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

Abstract

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.

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  • FREE Publisher Full Text
  • Authors

    Zhang L, Mori J, Wagg C, Lopaschuk GD

    Source

    FEBS letters 586:7 2012 Apr 5 pg 996-1003

    MeSH

    Animals
    Cell Nucleus
    Cyclin D1
    Cyclin-Dependent Kinase 4
    Diet, High-Fat
    E2F1 Transcription Factor
    Energy Metabolism
    Eukaryotic Initiation Factor-2
    Eukaryotic Initiation Factor-4E
    Male
    Mice
    Mice, Inbred C57BL
    Myocardium
    Oxidation-Reduction
    Phosphorylation
    Protein Processing, Post-Translational
    Protein Transport
    Protein-Serine-Threonine Kinases
    RNA, Messenger
    Signal Transduction
    Time Factors
    Up-Regulation

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22569253