Advanced search×

The role of class I histone deacetylase (HDAC) on gluconeogenesis in liver

Hiroshi Oiso, Noboru Furukawa, Mihoshi Suefuji, Seiya Shimoda, Akihiro Ito, Ryohei Furumai, Junichi Nakagawa, Minoru Yoshida, Norikazu Nishino, and Eiichi Araki

Biochem Biophys Res Commun 404(1):7 (2011) PMID 21108932

Hepatic gluconeogenesis is crucial for glucose homeostasis. Although sirtuin 1 (Sirt1) is implicated in the regulation of gluconeogenesis in the liver, the effects of other histone deacetylases (HDAC) on gluconeogenesis are unclear. The aim of this study was to identify the role of class I HDACs in hepatic gluconeogenesis. In HepG2 cells and the liver of mice, the expressions of phosphoenol pyruvate carboxykinase (PEPCK) and hepatocyte nuclear factor 4@a (HNF4@a) were significantly decreased by treatment with a newly designed class I HDAC inhibitor, Ky-2. SiRNA knockdown of HDAC1 expression, but not of HDAC2 or HDAC3, in HepG2 cells decreased PEPCK and HNF4@a expression. In HepG2 cells, insulin-stimulated phosphorylation of Akt and forkhead box O 1 (FoxO1) was increased by Ky-2. Pyruvate tolerance tests in Ky-2-treated high-fat-diet (HFD)-fed mice showed a marked reduction in blood glucose compared with vehicle-treated HFD mice. These data suggest that class I HDACs increase HNF4@a protein expression and the transcriptional activity of FoxO1, followed by the induction of PEPCK mRNA expression and gluconeogenesis in liver.

Copyright © 2011 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.bbrc.2010.11.086
Version: za2963e q8za9 q8zb8 q8zc5 q8zd6 q8ze6 q8zfe q8zg2

Similar articles you may find interesting…

  1. Genome-wide RNAi screen reveals disease-associated genes that are common to Hedgehog and Wnt signaling.
    Leni S Jacob, Xiaofeng Wu, ... Lawrence Lum

    Sci Signal 4(157):ra4 (2011) PMID 21266715

    We established previously unknown associations between these signaling pathways and genes linked to developmental malformations, diseases of premature tissue degeneration, and cancer. We identified functions in both pathways for the multitasking kinase Stk11 (also known as Lkb1), a tumor suppressor...
  2. A novel mitochondrial outer membrane protein, MOMA-1, that affects cristae morphology in Caenorhabditis elegans.
    Brian P BP Head, Miren M Zulaika, ... Alexander M AM van der Bliek

    Mol Biol Cell 22(6):831-41 (2011) PMID 21248201 PMCID PMC3057707

    We conclude that MOMA-1 and IMMT-1 act in the same pathway. It is likely that the observed effects on mitochondrial diameter are an indirect effect of disrupting cristae morphology....
    View PDF
  3. Uncovering the global host cell requirements for influenza virus replication via RNAi screening.
    Silke Stertz and Megan L Shaw

    Microbes Infect 13(5):516-25 (2011) PMID 21276872

    Influenza virus is reliant on numerous host cell functions during its replication cycle. RNA interference technology, applied on a genome-wide level, has identified human host factors that are necessary for efficient virus replication and provides new insight into how influenza virus...
    View PDF