Abstract
Thyroid hormone (T3) regulates various aspects of hepatic metabolism. C/EBPβ modulates the expression of multiple hepatic genes including those involved in hepatic gluconeogenesis. The conversion of pyruvate to acetyl‐CoA in mitochondria is catalyzed by the pyruvate dehydrogenase complex (PDC). Activity of PDC is decreased via phosphorylation by the pyruvate dehydrogenase kinases (PDK). Here we investigated the role of the CCAAT/enhancer‐binding protein β (C/EBPβ) in the T3 regulation of PDK4 gene expression. Our data indicate that C/EBPβ induces PDK4 gene expression and decreases PDC activity. This transcriptional induction is mediated through C/EBPβ binding sites in the PDK4 promoter. T3 increased C/EBPβ abundance in primary rat hepatocytes. Knockdown of C/EBPβ with siRNA diminished the T3 induction of the PDK4. Our data suggest that C/EBPβ is an important accessory factor for the T3 activation of PDK4 gene.
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