Deposition of docosahexaenoic acid (DHA) is limited in forebrain of young obese fa/fa Zucker rats fed a diet high in α-linolenic acid but devoid of DHA

January 1, 2010 Human Health and Nutrition Data 0 Comments

Deposition of docosahexaenoic acid (DHA) is limited in forebrain of young obese fa/fa Zucker rats fed a diet high in α-linolenic acid but devoid of DHA

Year: 2010
Authors: Zhao, J. Gillam, M.E. Gillam, M.E. Taylor, C.G. Weiler, H.A.
Publication Name: Journal of Nutritional Biochemistry
Publication Details: doi:10.1016/j.jnutbio.2010.06.012


Docosahexaenoic acid (DHA) is required for neurotransmitter synthesis and learning. Conversion of α-linolenic acid (ALA) to DHA is considered adequate to support brain function in youth, but it is unknown if brain DHA can be maintained in insulin resistant states. This study investigated brain fatty acid and desaturase activities in young insulin resistant Zucker rats on diets with and without DHA. Male fa/fa and lean rats were fed diets enriched with flaxseed (FXO, ALA: 35.5% fatty acids), menhaden (MO, DHA: 9.2%) or safflower oil (SO, linoleic acid: 54.1%) for 9 weeks, n=8 per diet per genotype. Compared to lean, the 15 week old fa/fa rats were obese (56% heavier) and insulin-resistant (N18-fold in homeostasis model assessment of insulin resistance). The forebrain of fa/fa rats had higher palmitoleic (16:1n-7) and dihomo-γ-linolenic (20:3n-6) acids, and higherΔ9, Δ6 but lower Δ5 (allP≤.006) desaturase indices than lean. The Δ9 and Δ6 desaturase indices positively, while the Δ5 negatively (all P≤.01) correlated with insulin resistance. TheΔ9 desaturase index positively correlated with adiposity index. The percentage of forebrain DHA of fa/fa rats was lower (P=.011) than lean rats when fed FXO diet while there was no difference (PN.05) between fa/fa and lean rats fed MO or SO diet. Thus, the alterations in the fatty acid and desaturase indices in the brain were consistent inhibited forebrain synthesis of DHA in the fa/fa rats. ALA may not have potential to effectively serve as a precursor for synthesizing DHA for youth forebrain during insulin resistance since Δ5 desaturase activity is limited. (Author`s abstract)
Insulin resistance syndrome is highly prevalent in Canadian youth. The brain is rich in DHA as a fundamental component of neural cell. To date, whether DHA is implicated in the reduced academic achievement of children has not been addressed. In humans with insulin resistance and related disorders there is a decrease in linoleic acid (18:2n-6) and an increase in palmitoleic (16:1n-7), γ-linolenic (18:3n-6) and dihomo-γ-linolenic (20:3n-6) acids. Under normal physiological conditions, the adult liver has ample capacity to synthesize DHA from circulating ALA. It is not clear if brain DHA can be sustained in obesity and insulin resistant states but it is suspected to be inadequate since people with insulin resistance have greater cognitive decline. It is unknown if Δ5 desaturase activity is sufficient to compensate for a diet devoid of DHA. The purpose of the present study was to compare the effects of dietary n-6 polyunsaturated fatty acid (PUFA) (linoleic acid, 18:2n6), n-3 PUFA (ALA, 18:3n-3) and n-3 long chain-PUFA (LC-PUFA; DHA, 22:6n-3) on the fatty acid composition and desaturases activities of three brain regions in obese and hyperinsulinemic young rats. In the present model of insulin resistance, lower forebrain DHA was observed in the fa/fa rats fed a diet with more than ample ALA (35.5 g/kg diet) for 9 weeks. Synthesis of DHA was likely the limiting factor rather than deposition of DHA since fa/fa rats fed a diet with preformed DHA had forebrain values not different from lean controls. These results thus suggest that ALA was not effective as a precursor for synthesizing DHA within young adult forebrain when accompanied by insulin resistance. The observation that the fa/fa rats did not have lower DHA in cerebellum or hippocampus regardless of diet suggests that the forebrain desaturase or elongase activity is vulnerable to hyperinsulinema. This supposition is supported by the lower Δ5 desaturase activity in fa/fa rat forebrain but not the other regions. In the present study, all three estimated desaturase activities of forebrain were altered in male fa/fa rats in comparison with lean rats. The altered desaturase indices of forebrain were significantly correlated with insulin resistance (HOMA-IR). The authors  speculate that hyperinsulinemia is able to stimulate synthesis of DHA in cerebellum and hippocampus, but not forebrain and suggest future work should aim to characterise insulin metabolism in each brain region under normal and hyperinsulinemic states to confirm if desaturase enzymes are also differentially affected. (Editor`s comments)

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