Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids

Organs are flexible as to which substrates they will use to maintain energy homeostasis. Under well-fed conditions, glucose is a preferred substrate for oxidation. During fasting, fatty acid oxidation will become a more important energy source. Glucose oxidation is decreased by fatty acids, a proces...

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2009-04, Vol.66 (7), p.1283-1294
Main Authors: Houten, S. M, Chegary, M, te Brinke, H, Wijnen, W. J, Glatz, J. F. C, Luiken, J. J. F. P, Wijburg, F. A, Wanders, R. J. A
Format: Article
Language:English
Subjects:
Acetyl-CoA Carboxylase - metabolism
AMP-activated protein kinase
AMP-Activated Protein Kinases - physiology
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell Hypoxia
Cells, Cultured
Energy Metabolism - physiology
Enzyme Activation
Fatty acids
Fatty Acids - physiology
Gene Expression Regulation, Enzymologic
Glucose
Glucose - metabolism
Hypoxia
Kinases
Life Sciences
Ligands
Metabolism
Myocytes, Cardiac - metabolism
Oxidation
Oxidation-Reduction
Peroxisome Proliferator-Activated Receptors - agonists
Protein Kinases - biosynthesis
pyruvate dehydrogenase
pyruvate dehydrogenase kinase 4
Rats
Research Article
Studies
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Summary:Organs are flexible as to which substrates they will use to maintain energy homeostasis. Under well-fed conditions, glucose is a preferred substrate for oxidation. During fasting, fatty acid oxidation will become a more important energy source. Glucose oxidation is decreased by fatty acids, a process in which the pyruvate dehydrogenase complex (PDH) and its regulator pyruvate dehydrogenase kinase 4 (PDK4) play important roles. It is currently unknown how energy status influences PDH activity. We show that AMP-activated protein kinase (AMPK) activation by hypoxia and AICAR treatment combined with fatty acid administration synergistically induce PDK4 expression. We provide evidence that AMPK activation modulates ligand-dependent activation of peroxisome proliferator-activated receptor. Finally, we show that this synergistic induction of PDK4 decreases cellular glucose oxidation. In conclusion, AMPK and fatty acids play a direct role in fuel selection in response to cellular energy status in order to spare glucose.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-009-9066-x