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Elevated Production of Docosahexaenoic Acid in Females: Potential Molecular Mechanisms

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  • Published:
Lipids

Abstract

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 A2 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.

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Abbreviations

ALA:

Alpha-linoleic acid

AMPK:

AMP-activated protein kinase

Ca2+-PLA2 :

Calcium-dependent phospholipase A2

CE:

Cholesteryl esters

COX:

Cyclooxygenase

CREB:

cAMP response element binding

D5D:

Delta-5 desaturase

D6D:

Delta-6 desaturase

DHA:

Docosahexaenoic acid

DPAn-3:

Docosapentaenoic acid, n-3

ELOVL:

Elongase of very long chain fatty acids

EPA:

Eicosapentaenoic acid

ER:

Estrogen receptor

ERK-MAPK:

Extracellular receptor kinase-mitogen activated protein kinase

FABP:

Fatty acid binding proteins

GPR30:

G-protein receptor 30

HUFA:

Highly unsaturated fatty acids

LNA:

Linoleic acid

MAPK:

Mitogen-activated protein kinase

PC:

Phosphatidyl choline

PE:

Phosphatidyl ethanolamine

PL:

Phospholipids

PLA2 :

Phospholipase A2

PPAR:

Peroxisome proliferator activated receptor

PPRE:

Peroxisome proliferator response element

PS:

Phosphatidyl serine

PUFA:

Polyunsaturated fatty acids

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  1. Laboratory of Nutritional and Nutraceutical Research, Department of Kinesiology, University of Waterloo, Waterloo, ON, N2L 3G1, Canada

    Alex P. Kitson, Chad K. Stroud & Ken D. Stark

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Kitson, A.P., Stroud, C.K. & Stark, K.D. Elevated Production of Docosahexaenoic Acid in Females: Potential Molecular Mechanisms. Lipids 45, 209–224 (2010). https://doi.org/10.1007/s11745-010-3391-6

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