Adaptive increase in pyruvate dehydrogenase kinase 4 during starvation is mediated by peroxisome proliferator-activated receptor alpha.

Abstract

Pyruvate dehydrogenase kinase isoform 4 (PDK4) is upregulated by starvation in many tissues of the body during starvation. This causes inactivation of the pyruvate dehydrogenase complex which blocks pyruvate oxidation and conserves lactate and alanine for gluconeogenesis. Enhanced PDK4 expression may be caused by the increase in free fatty acids that occurs during starvation. Free fatty acids can activate peroxisome proliferator-activated receptor alpha (PPARalpha), and activation of PPARalpha can promote PDK4 expression. This model is supported by the findings reported here that WY-14,643, a synthetic PPARalpha activator, increases PDK4 expression in wild-type mice but not in PPARalpha-null mice. Starvation likewise increases the expression of PDK4 in tissues of wild-type mice but not in tissues of PPARalpha-null mice. These findings document the functional importance of PPARalpha for PDK4 expression during starvation and suggest an important role for elevated free fatty acids in the induction.

• Authors: P Wu, J M Peters, R A Harris
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 287 Issue 2 Pg. 391-6 (Sep 21 2001) ISSN: 0006-291X [Print] United States
• PMID: 11554740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2001 Academic Press.

Chemical References

• Isoenzymes
• Peroxisome Proliferators
• Pyrimidines
• RNA, Messenger
• Receptors, Cytoplasmic and Nuclear
• Transcription Factors
• pirinixic acid
• Protein Kinases
• pyruvate dehydrogenase kinase 4

Topics

• Animals
• Enzyme Activation
• Heart (drug effects, physiology)
• Isoenzymes (genetics, metabolism)
• Kidney (drug effects, physiology)
• Male
• Mice
• Mice, Knockout
• Peroxisome Proliferators (pharmacology)
• Phenotype
• Protein Kinases (genetics, metabolism)
• Pyrimidines (pharmacology)
• RNA, Messenger (drug effects, metabolism)
• Receptors, Cytoplasmic and Nuclear (physiology)
• Starvation (enzymology, metabolism)
• Transcription Factors (physiology)