Effects of glucose metabolism on the 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, Matthew Brown

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1499-1510
Number of pages12
JournalJournal of Lipid Research
Volume48
Issue number7
DOIs
StatePublished - Jul 1 2007

Keywords

  • Gene expression
  • Glucokinase
  • Hepatic steatosis
  • Microarray analysis

ASJC Scopus subject areas

  • Endocrinology

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