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Coactivation of Foxa2 through Pgc-1beta promotes liver fatty acid oxidation and
triglyceride/VLDL secretion.
Authors Wolfrum C, Stoffel M
Submitted By Jan Breslow on 2/23/2009
Status Published
Journal Cell Metabolism
Year 2006
Date Published 2/1/2006
Volume : Pages 3(2) : 99
PubMed Reference
Abstract Forkhead transcription factor Foxa2 activates genes involved in hepatic lipid
metabolism and is regulated by insulin. Activation of Foxa2 in the liver leads
to increased oxidation and secretion of fatty acids in the form of
triacylglycerols (TAGs), a process impaired in type 2 diabetes. Here, we
demonstrate that Foxa2 is coactivated by PPARgamma coactivator beta (Pgc-1beta).
Adenoviral expression of Foxa2 and Pgc-1beta in livers of ob/ob mice results in
decreased hepatic TAG content and increased plasma TAG concentrations. In
addition, the concerted action of Foxa2/Pgc-1beta activates genes in
mitochondrial beta oxidation and enhances fatty acid metabolism. Furthermore,
Foxa2/Pgc-1beta induce the expression of microsomal transfer protein, thereby
increasing apoB-containing VLDL secretion. This process is inhibited by insulin
through a Foxa2-dependent mechanism. These data demonstrate that Foxa2/Pgc-1beta
regulate hepatic lipid homeostasis by affecting the clearance rate of fatty
acids through oxidation and/or secretion of lipids in response to insulin.

Complications









Genes
SymbolDescription
Foxa2forkhead box A2
Ppargc1bperoxisome proliferative activated receptor, gamma, coactivator 1 beta