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

Pengfei Wu, Jeffrey M. Peters, Robert Harris

Research output: Contribution to journalArticle

137 Citations (Scopus)

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 α (PPARα), and activation of PPARα can promote PDK4 expression. This model is supported by the findings reported here that WY-14,643, a synthetic PPARα activator, increases PDK4 expression in wild-type mice but not in PPARα-null mice. Starvation likewise increases the expression of PDK4 in tissues of wild-type mice but not in tissues of PPARα,-null mice. These findings document the functional importance of PPARα, for PDK4 expression during starvation and suggest an important role for elevated free fatty acids in the induction.

Original languageEnglish
Pages (from-to)391-396
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume287
Issue number2
DOIs
StatePublished - Sep 21 2001

Fingerprint

Peroxisome Proliferator-Activated Receptors
Starvation
Nonesterified Fatty Acids
Tissue
Pyruvate Dehydrogenase Complex
Gluconeogenesis
Pyruvic Acid
Alanine
pyruvate dehydrogenase (acetyl-transferring) kinase
pyruvate dehydrogenase kinase 4
Lactic Acid
Chemical activation
Oxidation

Keywords

  • Fatty acids
  • PPARα
  • Pyruvate dehydrogenase complex
  • Pyruvate dehydrogenase kinase
  • Starvation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Adaptive increase in pyruvate dehydrogenase kinase 4 during starvation is mediated by peroxisome proliferator-activated receptor α. / Wu, Pengfei; Peters, Jeffrey M.; Harris, Robert.

In: Biochemical and Biophysical Research Communications, Vol. 287, No. 2, 21.09.2001, p. 391-396.

Research output: Contribution to journalArticle

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N2 - 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 α (PPARα), and activation of PPARα can promote PDK4 expression. This model is supported by the findings reported here that WY-14,643, a synthetic PPARα activator, increases PDK4 expression in wild-type mice but not in PPARα-null mice. Starvation likewise increases the expression of PDK4 in tissues of wild-type mice but not in tissues of PPARα,-null mice. These findings document the functional importance of PPARα, for PDK4 expression during starvation and suggest an important role for elevated free fatty acids in the induction.

AB - 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 α (PPARα), and activation of PPARα can promote PDK4 expression. This model is supported by the findings reported here that WY-14,643, a synthetic PPARα activator, increases PDK4 expression in wild-type mice but not in PPARα-null mice. Starvation likewise increases the expression of PDK4 in tissues of wild-type mice but not in tissues of PPARα,-null mice. These findings document the functional importance of PPARα, for PDK4 expression during starvation and suggest an important role for elevated free fatty acids in the induction.

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