Elevated production of docosahexaenoic acid in females: potential molecular mechanisms.

Observational evidence suggests that in populations consuming low levels of n-3 highly unsaturated fatty acids, women have higher blood levels of docosahexaenoic acid (DHA; 22:3n-6) as compared with men. Increased conversion of alpha-linolenic acid (ALA; 18:3n-3) to DHA by females has been confirmed in fatty acid stable isotope studies. This difference in conversion appears to be associated with estrogen and some evidence indicates that the expression of enzymes involved in synthesis of DHA from ALA, including desaturases and elongases, is elevated in females. An estrogen-associated effect may be mediated by peroxisome proliferator activated receptor-alpha (PPARalpha), as activation of this nuclear receptor increases the expression of these enzymes. However, because estrogens are weak ligands for PPARalpha, estrogen-mediated increases in PPARalpha activity likely occur through an indirect mechanism involving membrane-bound estrogen receptors and estrogen-sensitive G-proteins. The protein kinases activated by these receptors phosphorylate and increase the activity of PPARalpha, as well as phospholipase A(2) and cyclooxygenase 2 that increase the intracellular concentration of PPARalpha ligands. This review will outline current knowledge regarding elevated DHA production in females, as well as highlight interactions between estrogen signaling and PPARalpha activity that may mediate this effect.