Abstract
Pyruvate dehydrogenase kinase 4 (PDK4) regulates pyruvate oxidation through the phosphorylation and inhibition of the pyruvate dehydrogenase complex (PDC). PDC catalyzes the conversion of pyruvate to acetyl‐CoA and is an important control point in glucose and pyruvate metabolism. PDK4 gene expression is stimulated by thyroid hormone (T3), glucocorticoids and long chain fatty acids. Here, we have identified two binding sites for the thyroid hormone receptor (TRß) in the promoter of the PDK4 gene. In addition, we have investigated the role of transcriptional coactivators and found that the peroxisome proliferator activated receptor gamma coactivator (PGC‐1α) enhances the T3 induction of PDK4. Addition of T3 to rat hepatocytes increased the abundance of the PGC‐1α and its association with the PDK4 promoter. Administration of T3 to hypothyroid rats increased PGC‐1α protein levels in the liver. In addition, we observed enhanced association of PGC‐1α not only with the PDK4 gene but also with phosphoenolpyruvate carboxykinase (PEPCK) and carnitine palmitoyltransferase 1a (CPT‐1a) genes. Knock‐down of PGC‐1α in rat hepatocytes reduced the T3 induction of PDK4, PEPCK and CPT‐1a genes. Our results indicate that T3 regulates PGC‐1α abundance and association with hepatic genes and in turn PGC‐1α is an important participant in the T3 induction of selected genes.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
