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.

Links

Publisher Full Text

Authors

Zhang L, Mori J, Wagg C, Lopaschuk GD

Institution

Cardiovascular Research Centre, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada.

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