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.

Key Findings:

In healthy humans, the liver has capacity to synthesize DHA from circulating ALA. This study compared the effects of dietary n-6 (linoleic acid), n-3 PUFA (ALA) and n-3 long chain-PUFA (LC-PUFA; DHA) on fatty acid composition and desaturases activities of three brain regions in obese and hyperinsulinemic young rats. Lower forebrain DHA was observed in the fa/fa rats fed a diet with sufficient ALA (35.5 g/kg diet) for 9 weeks most likely due to impaired synthesis of DHA. ALA appears not be an effective precursor for synthesizing DHA within young adult forebrain when accompanied by insulin resistance. 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. During hyperinsulinemia, synthesis of DHA in cerebellum and hippocampus is maintained, but is not in the forebrain.

ABSTRACT:

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)