Altered Lipid Metabolism in the Vitamin A Deficient Liver

We have compared the expression pattern of metabolic genes in vitamin A‐sufficient (VAS) versus vitamin A–deficient (VAD) liver using the Operon 32K Mouse Genome oligonucleotide (70‐mer) array (Operon Inc). The data were normalized in GeneSpring and further filtered using the Cross Gene Error Model. The microarray results were confirmed by real‐time PCR. Mice were made vitamin A deficient by placing them on the modified AIN‐93G diet without vitamin A on the tenth day of gestation and vitamin A deficiency was confirmed by HPLC analysis of retinol in serum and liver. We previously reported a decrease in expression of genes encoding enzymes of mitochondrial β‐oxidation, fatty acid ligase, acylCoA dehydrogenase (medium chain), and carnitine o‐palmitoyl transferase I in VAD liver. In our current analysis, the decrease in mitochondrial β‐oxidation is supported by a decrease of the carnitine synthesis from lysine. We also find a decrease in expression of genes encoding enzymes involved in peroxisomal β‐oxidation, acyl‐CoA oxidase, and in odd‐chain fatty acid oxidation, methylmalonyl‐CoA mutase. Bile acid synthesis is also affected as it includes β‐oxidation steps of side chains in the peroxisome. Consistent with the changes in gene expression above and our previous lipid data, the increase in lipid accumulation in the VAD liver was confirmed by Oil‐Red O staining. PPARα is a regulator of expression of genes involved in lipid metabolism. In addition to microarray and real‐time PCR analysis, Western blot analysis also shows a reduced PPARα level in the VAD liver.