Abstract
Studies indicate that the transcription factor peroxisome proliferator-activated receptors
(PPARs) regulate the activity of delta-6 and -5 desaturases and several key enzymes
of peroxisomal β-oxidation, including acyl-CoA oxidase. These enzymes are vital for
the synthesis of docosahexaenoic (22:6ω3; DHA) and osbond (22:5ω6, OA) acids. An activated
PPAR must form a hetrodimer with the obligate cofactor retinoid X receptor (RXR) to
interact with a peroxisome proliferator responsive element (PPRE) of a target gene
and to regulate transcriptional expression. The vitamin A metabolite, 9-cis retinoic acid, is the most potent ligand of RXR. We have tested the possibility that
deficiency of vitamin A would compromise tissue levels of both DHA and OA in rats.
Two groups of male Wistar rats were randomly distributed to receive vitamin A deficient
(VAD) or sufficient (VAS) diet. After seven weeks of feeding, the rats were killed
and colon and liver tissues removed for the analysis of fatty acids and antioxidant
status. The VAD compared to the VAS rats had elevated levels of arachidonic (AA, P<0.001), adrenic acid (22:4ω6, P<0.005) and OA (P<0.0001) and reduced proportions of eicosapentaenoic (EPA, docosapentaenoic (DPA),
DHA and total ω3 fatty (P<0.0001) in colon choline phosphoglycerides (CPG). Similarly, liver CPG of the VAD
rats had higher AA and adrenic acid and OA (P<0.0001), and lower EPA, DPA and DHA (P<0.0001) than the VAS rats. There was a similar fatty acid pattern in ethanolamine
phosphoglycerides of the colon and liver tissues. These differences could not be explained
by the conventional microsomal-peroxisomal pathway of the synthesis of the long-chain
ω6 and ω3 polyunsaturated fatty acids. We postulate that deficiency of dietary vitamin
A and the consequential depletion of retinoids inhibits DHA, and enhances OA, synthesis
by differential effects on the independent synthetic pathways of the two fatty acids
in the mitochondria. Various studies have documented that both DHA and vitamin A are
vital for optimal visual and neural development and function. There is a need for
further investigations to elucidate how vitamin A deficiency reduces membrane DHA
level, and to delineate the synergistic effect of the two nutrients on vision, learning
and memory.
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Article info
Publication history
Published online: October 11, 2004
Accepted:
July 29,
2004
Received:
May 12,
2004
Identification
Copyright
© 2004 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
