title: Altered lipid catabolism in the vitamin A deficient liver.
abstract: The transcriptome pattern of metabolic genes in vitamin A deficient (VAD) liver has been compared to the vitamin A-sufficient (VAS) state using the Mouse 32k oligonucleotide (70mer) array. In VAD liver there was a decrease in expression of genes encoding enzymes of mitochondrial fatty acid (FA) oxidation; these genes included fatty acyl CoA ligase, carnitine o-palmitoyl transferase 1, medium chain acyl-CoA dehydrogenase, 3-ketoacyl CoA thiolase, and citrate synthase. Particularly affected was peroxisome metabolism, as genes encoding enzymes of peroxisomal FA oxidation and transport proteins were differentially expressed. These genes included those encoding acyl-CoA oxidase 1, the peroxisomal bifunctional enzyme, peroxisomal thiolase, and carnitine o-octanoyl transferase, the enzyme involved in shuttling FAs from the peroxisome to the mitochondrion. Most genes that were differentially expressed with chronic vitamin A depletion were responsive to treatment with all-trans retinoic acid (RA). Consistent with the decreased expression of genes involved in FA oxidation, we found an increase in hepatic macrocytic lipid accumulation and triglyceride levels. The relevant nuclear receptor gene that was differentially expressed in the VAD liver was that encoding the peroxisome proliferator-activated receptor (PPAR) alpha, the mRNA levels for which were decreased in VAD liver and increased with all-trans RA treatment. Down regulation of the PPAR alpha gene is the likely cause of the altered expression pattern of the above metabolic genes in VAD liver.
authors.affiliation: Departments of Nutritional Sciences and Molecular and Cellular Biology, The University of Connecticut, 3624 Horsebarn Hill Road Extension, Storrs, CT 06269, USA.
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Kang
authors.forename: Gautam Reddy
authors.initials: GR
authors.lastname: Bhimidi
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Odom
authors.forename: Pierre-Jacques
authors.initials: PJ
authors.lastname: Brun
authors.forename: Maria-Luz
authors.initials: ML
authors.lastname: Fernandez
authors.forename: Mary M
authors.initials: MM
authors.lastname: McGrane
mesh_terms: D000818:Animals; D004032:Diet; D020869:Gene Expression Profiling; D050356:Lipid Metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D014802:Vitamin A Deficiency / Q000378:metabolism*