Dietary n-3 PUFA deprivation for 15 weeks upregulates elongase and desaturase expression in rat liver but not brain

Abstract

Fifteen weeks of dietary n-3 PUFA deprivation increases coefficients of conversion of circulating alinolenic acid (a-LNA; 18:3n-3) to docosahexaenoic acid (DHA; 22:6n-3) in rat liver but not brain. To determine whether these increases reflect organ differences in enzymatic activities, we examined brain and liver expression of converting enzymes and of two of their transcription factors, peroxisome proliferator-activated receptor a (PPARa) and sterol-regulatory element binding protein-1 (SREBP-1), in rats fed an n-3 PUFA "adequate" (4.6% a-LNA of total fatty acid, no DHA) or "deficient" (0.2% a-LNA, no DHA) diet for 15 weeks after weaning. In rats fed the deficient compared with the adequate diet, mRNA and activity levels of #5 and #6 desaturases and elongases 2 and 5 were upregulated in liver but not brain, but liver PPARa and SREBP-1 mRNA levels were unchanged. In rats fed the adequate diet, enzyme activities generally were higher in liver than brain. Thus, differences in conversion enzyme expression explain why the liver has a greater capacity to synthesize DHA from circulating a-LNA than does the brain in animals on an adequate n-3 PUFA diet and why liver synthesis capacity is increased by dietary deprivation. These data suggest that liver n-3 PUFA metabolism determines DHA availability to the brain when DHA is absent from the diet.-Igarashi, M., K. Ma, L. Chang, J. M. Bell, and S. I. Rapoport. Dietary n-3 PUFA deprivation for 15 weeks upregulates elongase and desaturase expression in rat liver but not brain.

Linoleic and α-linolenic acid as precursor and inhibitor for the synthesis of long-chain polyunsaturated fatty acids in liver and brain of growing pigs

“…High ALA intake resulted in a significant increase in ELOVL2 mRNA expression, which may relate to the strong increase in the content of DPA, a product of ELOVL2, in both frontal cortex and hippocampus. On the other hand, we did not observe an effect on mRNA expression of D6 and D5 desaturase and ELOVL5 in the hippocampus that agrees with studies in rat brain (Igarashi et al, 2007a).…”

“…Unfortunately, we did not have the standards in order to establish whether this was paralleled by a positive effect on the content of c24:5 n-3 and c24:4 n-6 as well. Fatty acid-dependent changes in hepatic ELOVL2 expression have also been reported in rat and salmon (Igarashi et al, 2007a;Morais et al, 2009).…”

“…Other studies in rat brain showed that ALA after uptake from the circulation across the blood-brain barrier will be mainly oxidized and only a small fraction is converted to DHA (DeMar et al, 2005;Igarashi et al, 2007b). The activity of desaturation and elongation are higher in liver in comparison with brain (Igarashi et al, 2007a). This suggests that most DHA in the brain is derived from another source, such as liver, intestine (diet) and/or adipose tissue.…”

“…DHA can be generated from EPA that requires an additional chain-shortening step (i.e. b-oxidation) in the peroxisome (Sprecher, 2000;Igarashi et al, 2007a). The conversion of n-6 LC-PUFA from LA (resulting in the production of ARA) sharing the same enzymes resulting in enzymatic competition between the biosynthetic pathways of n-3 and n-6 LC-PUFA.…”

Interaction of brain fatty acid-binding protein with the polyunsaturated fatty acid environment as a potential determinant of poor prognosis in malignant glioma

“…In cases of ω-3 PUFA deficiency (greatly reduced ALA, no DHA) for 15 weeks, brain DHA content was reduced by 37% [37,43]. To maintain brain DHA content, brain DHA metabolism, as measured by iPLA 2 and COX-1, was reduced in ω-3 PUFA-deficient rats.…”