Submitted on February 16, 2007
Revised on April 2, 2007
Accepted on April 20, 2007
Effects of glucose metabolism on regulation of genes of fatty acid synthesis and triglyceride secretion in the liver
Núria Morral, 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 46202
Corresponding Author: nmorralc{at}iupui.edu
Glucose disposal induces a signal that modulates 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-pyruvic kinase (L-PK), malic enzyme, fatty acid synthase (FAS), and stearoyl-CoA desaturase 1, were enhanced multiple fold, while genes involved in mitochondrial fatty acid oxidation and the Krebs cycle were down-regulated. 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 DGAT1, DGAT2 and MTP, were observed. Overall, our data suggests that the gene expression pattern induced by glucose metabolism favors fatty acid storage in the liver rather than secretion into the circulation.
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