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Elevated Production of Docosahexaenoic Acid in Females: Potential Molecular Mechanisms
Author(s) -
Kitson Alex P.,
Stroud Chad K.,
Stark Ken D.
Publication year - 2010
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-010-3391-6
Subject(s) - docosahexaenoic acid , estrogen , estrogen receptor , medicine , endocrinology , peroxisome proliferator activated receptor , biology , nuclear receptor , receptor , biochemistry , fatty acid , chemistry , polyunsaturated fatty acid , transcription factor , cancer , breast cancer , gene
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‐α (PPARα), as activation of this nuclear receptor increases the expression of these enzymes. However, because estrogens are weak ligands for PPARα, estrogen‐mediated increases in PPARα 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 PPARα, as well as phospholipase A 2 and cyclooxygenase 2 that increase the intracellular concentration of PPARα ligands. This review will outline current knowledge regarding elevated DHA production in females, as well as highlight interactions between estrogen signaling and PPARα activity that may mediate this effect.