CCAAT/enhancer binding protein-β is a transcriptional regulator of peroxisome-proliferator-activated receptor-γ coactivator-1α in the regenerating liver

Haitao Wang, T. Harshani Peiris, A. Mowery, John Le Lay, Yan Gao, Linda E. Greenbaum

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The transcriptional coactivator peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) is induced in the liver in response to fasting and coordinates the activation of targets necessary for increasing energy production for gluconeogenesis and ketogenesis. After partial hepatectomy, the liver must restore its mass while maintaining metabolic homeostasis to ensure survival. Here we report that PGC-1α is rapidly and dramatically induced after hepatectomy, with an amplitude of induction that exceeds the fasting response. Maximal activation of PGC-1α after hepatectomy is dependent on the basic leucine zipper transcription factor, CCAAT/enhancer binding protein-β (C/EBPβ), a critical factor in hepatocyte proliferation. We demonstrate in vivo C/EBPβ binding to C/EBP and cAMP response element sites in the PGC-1α promoter and show that the C/EBP site is essential for PGC-1α activation. Expression of the PGC-1α target, carnitine palmitoyl transferase 1a, the rate-limiting enzyme in fatty acid β-oxidation, and of long-chain acyl-coenzyme A dehydrogenase, an enzyme involved in β-oxidation of long chain fatty acids, was significantly reduced in C/EBPβ-/- livers after hepatectomy. These findings identify C/EBPβ as a direct activator of PGC-1α in the regenerating liver. The demonstration of a functional link between C/EBPβ and PGC-1α activation provides a likely mechanism for how upstream signaling pathways in the regenerating liver can enable the adaptation to the changed metabolic status.

Original languageEnglish (US)
Pages (from-to)1596-1605
Number of pages10
JournalMolecular Endocrinology
Volume22
Issue number7
DOIs
StatePublished - Jul 1 2008
Externally publishedYes

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CCAAT-Enhancer-Binding Proteins
Peroxisome Proliferator-Activated Receptors
Hepatectomy
Liver
Fasting
Long-Chain Acyl-CoA Dehydrogenase
Fatty Acids
Basic-Leucine Zipper Transcription Factors
Gluconeogenesis
Carnitine
Response Elements
Enzymes
Transferases
Protein Binding
Hepatocytes
Homeostasis
Binding Sites

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

CCAAT/enhancer binding protein-β is a transcriptional regulator of peroxisome-proliferator-activated receptor-γ coactivator-1α in the regenerating liver. / Wang, Haitao; Peiris, T. Harshani; Mowery, A.; Lay, John Le; Gao, Yan; Greenbaum, Linda E.

In: Molecular Endocrinology, Vol. 22, No. 7, 01.07.2008, p. 1596-1605.

Research output: Contribution to journalArticle

Wang, Haitao ; Peiris, T. Harshani ; Mowery, A. ; Lay, John Le ; Gao, Yan ; Greenbaum, Linda E. / CCAAT/enhancer binding protein-β is a transcriptional regulator of peroxisome-proliferator-activated receptor-γ coactivator-1α in the regenerating liver. In: Molecular Endocrinology. 2008 ; Vol. 22, No. 7. pp. 1596-1605.
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