Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression

doi:10.1073/pnas.0402342101

Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression

^*Laboratory of Functional Genomics, Biological Research Center, Hungarian Academy of Sciences, H-6701, Szeged, Hungary; ^†Department of Food Science, RMIT University, Melbourne, Victoria 3000, Australia; ^‡Howard Florey Institute of Experimental Physiology and Medicine, and ^§Department of Vision Science, University of Melbourne, Melbourne, Victoria 3010, Australia; and ^¶School of Aquatic and Fishery Sciences, University of Washington, Seattle, WA 98195

Contributed by John E. Halver, April 2, 2004

Abstract

Polyunsaturated fatty acids (PUFA) are essential structural components of the central nervous system. Their role in controlling learning and memory has been well documented. A nutrigenomic approach with high-density microarrays was used to reveal brain gene-expression changes in response to different PUFA-enriched diets in rats. In aged rats fed throughout life with PUFA-enriched diets, genes with altered expressions included transthyretin, α-synuclein, and calmodulins, which play important roles in synaptic plasticity and learning. The effect of perinatal omega-3 PUFA supply on gene expression later in life also was studied. Several genes showed similar changes in expression in rats fed omega-3-deficient diets in the perinatal period, regardless of whether they or their mothers were fed omega-3 PUFA-sufficient diets after giving birth. In this experiment, among the down-regulated genes were a kainate glutamate receptor and a DEAD-box polypeptide. Among the up-regulated genes were a chemokine-like factor, a tumor necrosis factor receptor, and cytochrome c. The possible involvement of the genes with altered expression attributable to different diets in different brain regions in young and aged rats and the possible mode of regulatory action of PUFA also are discussed. We conclude that PUFA-enriched diets lead to significant changes in expression of several genes in the central nervous tissue, and these effects appear to be mainly independent of their effects on membrane composition. The direct effects of PUFA on transcriptional modulators, the downstream developmentally and tissue-specifically activated elements might be one of the clues to understanding the beneficial effects of the omega-3 PUFA on the nervous system.

Footnotes

↵ ∥ To whom correspondence should be addressed at: Laboratory of Functional Genomics, Biological Research Center, Hungarian Academy of Sciences, P.O. Box 521, H-6701, Szeged, Hungary. E-mail: pusi{at}brc.hu.
Abbreviations: PUFA, polyunsaturated fatty acid; LA, linoleic acid; ALA, α-linolenic acid; FA, fatty acid; AA, arachidonic acid; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; PPAR, peroxisome proliferator-activated receptor; AD, Alzheimer's disease; Aβ, amyloid β peptide; FABP, FA binding protein; LXR, liver X receptor; SREBP, sterol regulatory element-binding protein.