Microarray analysis indicates an important role for FABP5 and putative novel FABPs on a Western-type diet.
Liver parenchymal cells play a dominant role in hepatic metabolism and thereby total body cholesterol homeostasis. To gain insight into the specific pathways and genes involved in the response of liver parenchymal cells to increased dietary lipid levels under atherogenic conditions, 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. Using ABI Mouse Genome Survey Arrays, we were able to detect 7,507 genes (28% of the total number on an 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, because 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 the 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 stimulated glycolysis and lipogenesis pathways, resulting in a steady, more atherogenic serum lipoprotein profile (increased VLDL/LDL).
Hoekstra
Menno
M
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, 2300 RA Leiden, The Netherlands. hoekstra@lacdr.leidenuniv.nl
Stitzinger
Miranda
M
van Wanrooij
Eva J A
EJ
Michon
Ingrid N
IN
Kruijt
J Kar
JK
Kamphorst
J
J
Van Eck
M
M
Vreugdenhil
E
E
Van Berkel
Theo J C
TJ
Kuiper
Johan
J
D000595:Amino Acid Sequence; D000821:Animal Feed; D000818:Animals; D004032:Diet; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D008055:Lipids / Q000097:blood; D008099:Liver / Q000166:cytology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011973:Receptors, LDL / Q000172:deficiency
C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; D008055:Lipids; D011973:Receptors, LDL