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

Núria Morral¹^,*^,^,, Howard J. Edenberg^*^,, Scott R. Witting^*^,, Jennifer Altomonte, Tearina Chu^** and Matthew Brown^*

^* Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN
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

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 transcriptionalregulation of genes involved in the glycolysis and lipogenesispathways. To investigate the role of glucose metabolism on hepaticgene expression independently from insulin action, we overexpressedglucokinase, 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 suchas liver-type pyruvate kinase, malic enzyme, fatty acid synthase,and stearoyl-CoA desaturase 1 were enhanced multiple-fold, whereasgenes involved in mitochondrial fatty acid oxidation and theKrebs cycle were downregulated. Despite the increase in expressionof fatty acid synthesis genes and the presence of steatosis,no major alterations to the levels of genes involved in VLDLassembly and secretion, such as diacylglycerol acyltransferases1 and 2 and microsomal triglyceride transfer protein, were observed.Overall, our data suggest that the gene expression pattern inducedby glucose metabolism favors fatty acid storage in the liverrather than secretion into the circulation.

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

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