Retroconversion and metabolism of [13C]22:6n−3 in humans and rats after intake of a single dose of [13C]22:6n−3-triacylglycerols

Abstract

The apparent retroconversion of docosahexaenoic acid (22:6n-3) to eicosapentaenoic acid (20:5n-3) and docosapentaenoic acid (22:5n-3) was studied in vivo, in rats and humans, after they ingested a single dose of triacylglycerols containing [13C]22:6n-3 ([13C]22:6-triacylglycerol), without 22:6n-3 dietary supplementation. The amount of apparent retroconversion and the distribution of the three n-3 polyunsaturated fatty acids (PUFAs) in plasma lipid classes were followed as a function of time by measuring the appearance of 13C in these PUFAs with gas-chromatography combustion-isotope ratio mass spectrometry. This [13C]22:6n-3 retroconversion, calculated by summing the amounts of [13C]22:5n-3 and [13C]20:5n-3 in plasma lipids, was lower in humans than in rats, reaching a maximum of approximately 9% of the total plasma [13C]22:6n-3 in rats, but only 1.4% in humans. The incorporation of [13C]22:6n-3 and [13C]22:5n-3 in lipid classes followed their endogenous distribution with a maximal accumulation in phospholipids, but a low incorporation into cholesterol esters (CEs), whereas [13C]20:5n-3 was equally present in phospholipids and CEs. The ratio of the amount of HDL-CE to HDL-phosphatidylcholine for [13C]20:5n-3 was higher than for [13C]22:6n-3, indicating a selectivity of the lecithin-cholesterol acyltransferase enzyme with regard to these PUFAs, which may be related to the differences in their biological properties after fish oil feeding. The occurrence of a weak basal 22:6n-3 retroconversion in humans supports feeding this pure PUFA in cases in which 20:5n-3 presents undesirable side effects and when specific alterations of blood lipids are expected.

Effects of essential fatty acid deficiency and supplementation with docosahexaenoic acid (DHA; 22:6n-3) on cellular fatty acid compositions and fatty acyl desaturation in a cell culture model

“…In effect, retroconversion of DHA, which requires saturation of the Δ 4 double bond by 2,4-enoyl-CoA reductase and peroxisomal chain shortening via limited β-oxidation, appears to be inhibited by EFA deficiency. Retroconversion of DHA to 22:5n-3 and EPA has been observed previously in various animal tissues [30][31][32] and retroconversion of DHA to 22:5n-3 and EPA, and 22:5n-3 to EPA has been reported in various cells in culture. 22,[33][34][35] In contrast, in rat U III (uterine stromal) cells, which show higher levels of DHA production from 18:3n-3 than most other cell lines, there was no significant retroconversion of DHA, added at 5 µM.…”

Effect of dietary supplementation with increasing doses of docosahexaenoic acid on neutrophil lipid composition and leukotriene production in human healthy volunteers

“…Second, the proportion of EPA significantly increased after the daily intake of 1600 mg DHA, and was significantly correlated to DHA content. Since the dietary supplementation was free of EPA, the data suggest that DHA was likely retroconverted to EPA as previously described (19) . Although the design of the present study did not allow determination of which dose of DHA initiates the retroconversion of DHA to EPA, the present data suggest that it might occur only for high doses of DHA.…”

Influence of three rapeseed oil-rich diets, fortified with α-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid on the composition and oxidizability of low-density lipoproteins: results of a controlled study in healthy volunteers

“…Such a retroconversion has been documented in several supplementation studies with purified DHA Holub, 1996, 1997;Vidgren et al, 1997;Hansen et al, 1998) and in one study of DHA metabolism using [ 13 C]DHA in humans (Brossard et al, 1996). In summary, an increased dietary intake of ALA, EPA or DHA led to a significant enrichment of the respective fatty acid in the LDL particles.…”