Br J Nutr., 2018., doi: 10.1017/S0007114518003252.

Low-linoleic acid diet and oestrogen enhance the conversion of α-linolenic acid into DHA through modification of conversion enzymes and transcription factors.

Kim D Choi JE Park Y.

Abstract

Conversion of α-linolenic acid (ALA) into the longer chain n-3 PUFA has been suggested to be affected by the dietary intake of linoleic acid (LA), but the mechanism is not well known. Therefore, the purpose of this study was to evaluate the effect of a low-LA diet with and without oestrogen on the fatty acid conversion enzymes and transcription factors. Rats were fed a modified American Institute of Nutrition-93G diet with 0% n-3 PUFA or ALA, containing low or high amounts of LA for 12 weeks. At 8 weeks, the rats were injected with maize oil with or without 17β-oestradiol-3-benzoate (E) at constant intervals for the remaining 3 weeks. Both the low-LA diet and E significantly increased the hepatic expressions of PPAR-α, fatty acid desaturase (FADS) 2, elongase of very long chain fatty acids 2 (ELOVL2) and ELOVL5 but decreased sterol regulatory element binding protein 1. The low-LA diet, but not E, increased the hepatic expression of FADS1, and E increased the hepatic expression of oestrogen receptor-α and β. The low-LA diet and E had synergic effects on serum and liver levels of DHA and on the hepatic expression of PPAR-α. In conclusion, the low-LA diet and oestrogen increased the conversion of ALA into DHA by upregulating the elongases and desaturases of fatty acids through regulating the expression of transcription factors. The low-LA diet and E had a synergic effect on serum and liver levels of DHA through increasing the expression of PPAR-α.

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Key Points

Oestrogen, dietary content of ALA, fatty acid composition of the diet and dietary content of linoleic acid, (LA, 18 : 2n-6) have been shown to affect the conversion of ALA into DHA. It has been shown that ALA increases hepatic expressions of FADS2, FADS1, ELOVL5, ELOVL2 and peroxisomal acyl-coenzyme A oxidase 1 (ACOX1) through regulating PPAR-α. In addition, an increased LA:ALA ratio decreases the conversion of ALA into EPA and DHA in rat. The purpose of this study was to investigate the hypothesis that a high-LA diet decreases the conversion of ALA to EPA and DHA by reducing the expression of the conversion enzymes by modulating the expression of transcription factors, while the ALA content is the same in low and high-LA diets. The synergic effect of oestrogen and a low-LA diet on the increased conversion of ALA into EPA and DHA in ovariectomised rats. This study demonstrated that a high-LA diet reduced protein expression of FADS2, FADS1, ELOVL5 and ELOVL2 through increased expression of PPAR-α and decreased expression of SREBP1 in ovariectomised rats, suggesting that a high-LA diet decreased the conversion of ALA into EPA and DHA. The high-LA diet had no effect on ACOX1 expression in the present study.  The high-LA diet decreased the conversion of ALA into EPA and DHA by reducing the expression of FADS and elongases through modification of transcription factors such as PPAR-α and SREBP1. In addition, oestrogen enhanced the conversion of ALA into DHA by modifying conversion enzymes and transcription factors, particularly PPAR-α, synergically with the low-LA diet.