Submitted on February 23, 2006
Revised on July 28, 2006
Accepted on August 2, 2006
Microarray analysis indicates an important role for FABP5 and putative novel fatty acid binding proteins in the primary response of liver parenchymal cells from LDL receptor deficient mice to a Western-type diet
Menno Hoekstra, Miranda Stitzinger, Eva J. A. van Wanrooij, Ingrid N. Michon, J. Kar Kruijt, Jessica Kamphorst, Miranda Van Eck, Erno Vreugdenhil, Theo J. C. Van Berkel, and Johan Kuiper
Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden, Zuid-Holland 2300 RA
Corresponding Author: hoekstra{at}lacdr.leidenuniv.nl
Liver parenchymal cells play a dominant role in hepatic metabolism and thereby total body cholesterol homeostasis. To gain insight in the specific pathways and genes involved in the response of liver parenchymal cells to increased dietary lipid levels under an atherogenic condition, in the current study changes in parenchymal cell gene expression upon feeding a Western-type diet for 0, 2, 4, and 6 weeks were determined using microarray analysis in LDL receptor deficient mice, an established atherosclerotic animal model. By using ABI Mouse Genome Survey Arrays we were able to detect 7507 genes (28% of total number on array) that were expressed in parenchymal cells isolated from livers of LDL receptor deficient mice at every time point investigated. Time-dependent gene expression profiling identified fatty acid binding protein 5 (FABP5) and four novel FABP5-like transcripts located on chromosomes 2, 8, and 18 as important proteins in the primary response of liver parenchymal cells to Western-type diet feeding, since their expression was 16- to 22-fold increased within the first 2 weeks on the Western-type diet. The rapid substantial increase in gene expression suggests that these FABPs may play an important role in the primary protection against cellular toxicity of cholesterol, free fatty acids and/or lipid oxidants. Furthermore, as a secondary response to the Western-type diet, liver parenchymal cells of LDL receptor deficient mice stimulate glycolysis and lipogenesis pathways, resulting in a steady more atherogenic serum lipoprotein profile (increased VLDL/LDL).
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
