Global effects of vitamin A deficiency on gene expression in rat liver: evidence for hypoandrogenism.
Vitamin A (retinol) metabolites are ligands for transcription factors that regulate many genes. The liver is the main storage depot for retinol and plays a role in vitamin A homeostasis. To better understand the effects of vitamin A deficiency on liver gene expression, we produced retinol deficiency in male rats by feeding a diet low in retinol for 53 days after weaning and examined the effects on gene expression in liver using Affymetrix oligonucleotide microarrays. We detected expression of 41% of the 8799 probe sets represented on the RGU-34A GeneChips. Vitamin A deficiency resulted in major changes in liver gene expression: 805 genes (22% of all genes detected) differed at P<or=.05 (false discovery rate <0.143). Genes involved in fatty acid metabolism, peroxisomal function, glycolysis, glutamate metabolism and the urea cycle were altered. The expression of many sexually dimorphic genes was altered toward a feminized or senescent pattern of gene expression in the liver. Retinol deficiency also produces a shift toward increased protein and fat catabolism and decreased fatty acid synthesis.
McClintick
Jeanette N
JN
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202-5251, USA.
Crabb
David W
DW
Tian
Huijun
H
Pinaire
Jane
J
Smith
Jennifer R
JR
Jerome
Ronald E
RE
Edenberg
Howard J
HJ
D000728:Androgens / Q000172:deficiency*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D004032:Diet; D020869:Gene Expression Profiling; D008099:Liver / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014802:Vitamin A Deficiency / Q000378:metabolism*
D000728:Androgens; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; C493085:Cyp2c7 protein, rat; D000072467:Cytochrome P450 Family 2