J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M700090-JLR200 on April 21, 2007

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Journal of Lipid Research, Vol. 48, 1499-1510, July 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Effects of glucose metabolism on the regulation of genes of fatty acid synthesis and triglyceride secretion in the liverboxs

Núria Morral1,*,{dagger},§, Howard J. Edenberg*,{dagger}, Scott R. Witting*,{dagger}, Jennifer Altomonte§, Tearina Chu** and Matthew Brown*

* Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
{dagger} Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN
§ Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY
** Microarray Shared Research Facility, Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY

boxs The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of an appendix.

Published, JLR Papers in Press, April 21, 2007.

1 To whom correspondence should be addressed. e-mail: nmorralc{at}iupui.edu

Glucose disposal induces a signal that modulates the transcriptional regulation of genes involved in the glycolysis and lipogenesis pathways. To investigate the role of glucose metabolism on hepatic gene expression independently from insulin action, we overexpressed glucokinase, the limiting enzyme in the glycolysis pathway, in the liver of streptozotocin-induced type 1 diabetic rats. By microarray analysis, we observed that critical genes such as liver-type pyruvate kinase, malic enzyme, fatty acid synthase, and stearoyl-CoA desaturase 1 were enhanced multiple-fold, whereas genes involved in mitochondrial fatty acid oxidation and the Krebs cycle were downregulated. Despite the increase in expression of fatty acid synthesis genes and the presence of steatosis, no major alterations to the levels of genes involved in VLDL assembly and secretion, such as diacylglycerol acyltransferases 1 and 2 and microsomal triglyceride transfer protein, were observed. Overall, our data suggest that the gene expression pattern induced by glucose metabolism favors fatty acid storage in the liver rather than secretion into the circulation.

Supplementary key words gene expression • hepatic steatosis • glucokinase • microarray analysis


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Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.