Gender affects liver desaturase expression in a rat model of n−3 fatty acid repletion☆

Abstract 

Dietary n−3 polyunsaturated fatty acids (PUFA) are major components of cell membranes and have beneficial effects on human health. Docosahexaenoic acid (DHA; 22:6n−3) is the most biologically important n−3 PUFA and can be synthesized from its dietary essential precursor, α-linolenic acid (ALA; 18:3n−3). Gender differences in the efficiency of DHA bioconversion have been reported, but underlying molecular mechanisms are unknown. We compared the capacity for DHA synthesis from ALA and the expression of related enzymes in the liver and cerebral cortex between male and female rats. Wistar rats, born with a low-DHA status, were supplied with a suboptimal amount of ALA from weaning to 8 weeks of age. Fatty acid composition was determined by gas chromatography, the mRNA expression of different genes involved in PUFA metabolism was determined by RT-PCR (low-density array) and the expression of proteins was determined by Western blot analysis. At 8 weeks, DHA content was higher (+20 to +40%) in each phospholipid class of female livers compared to male livers. The “Δ4,” Δ5 and Δ6 desaturation indexes were 1.2–3 times higher in females than in males. The mRNA expression of Δ5- and Δ6-desaturase genes was 3.8 and 2.5 times greater, respectively, and the Δ5-desaturase protein was higher in female livers (+50%). No gender difference was observed in the cerebral cortex. We conclude that female rats replete their DHA status more readily than males, probably due to a higher expression of liver desaturases. Our results support the hypothesis on hormonal regulation of PUFA metabolism, which should be taken into account for specific nutritional recommendations.

Abbreviations: AA, arachidonic acid [20:4n−6], ALA, α-linolenic acid [18:3n−3], ACOX1, acyl-coenzyme A oxidase 1, DHA, docosahexaenoic acid [22:6n−3], n−3 DPA, n−3 docosapentaenoic acid [22:5n−3], n−6 DPA, n−6 docosapentaenoic acid [22:5n−6], EPA, eicosapentaenoic acid [20:5n−3], EPG, ethanolamine phosphoglycerolipid, FABP, fatty acid binding protein, FADS1, fatty acid desaturase 1, FADS2, fatty acid desaturase 2, LA, linoleic acid [18:2n−6], MFP1, multifunctional protein 1, MFP2, multifunctional protein 2, PPAR, peroxisome proliferator-activated receptor, PC, phosphatidylcholine, PS, phosphatidylserine, PUFA, polyunsaturated fatty acids, RIN, RNA integrity number, RQ, relative quantities, RXR, retinoid X receptor, SREBP1c, sterol-regulatory element-binding protein 1c, TLDA, TaqMan Low-Density Array

Keywords: n−3 PUFA, Gender, Desaturases, Docosahexaenoic acid, Liver, Rats