Coenzyme A-mediated degradation of pyruvate dehydrogenase kinase 4 promotes cardiac metabolic flexibility after high-fat feeding in mice.

ABSTRACT: Cardiac energy is produced primarily by oxidation of fatty acids and glucose, with the relative contributions of each nutrient being sensitive to changes in substrate availability and energetic demand. A major contributor to cardiac metabolic flexibility is pyruvate dehydrogenase (PDH), which converts glucose-derived pyruvate to acetyl-CoA within the mitochondria. PDH is inhibited by phosphorylation dependent on the competing activities of pyruvate dehydrogenase kinases (PDK1-4) and phosphatases (PDP1-2). A single high-fat meal increases cardiac PDK4 content and subsequently inhibits PDH activity, reducing pyruvate utilization when abundant fatty acids are available. In this study, we demonstrate that diet-induced increases in PDK4 are reversible and characterize a novel pathway that regul

SUBMITTER: Schafer C 

PROVIDER: S-EPMC5936801 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature