Postprandial metabolism of docosapentaenoic acid (DPA, 22:5n−3) and eicosapentaenoic acid (EPA, 20:5n−3) in humans
Introduction
The essential fatty acid alpha-linoleic acid (ALA, 18:3n−3) can be metabolized in vivo by desaturation and elongation enzymes to form a series of polyunsaturated fatty acids (PUFA) of the n−3 series. In addition to potentially being synthesised from ALA, eicosapentaenoic acid (EPA, 20:5n−3), docosahexaenoic acid (DHA, 22:6n−3) and docosapentaenoic acid (DPA, 22:5n−3) are provided from diet, mainly from fish and fish oil products and to a lesser extent from ruminant meats. Currently, there is much information on the metabolism of both EPA and DHA, while less is known about the metabolism of DPA.
In vivo, DPA is formed by chain elongation of EPA by the action of fatty acid elongases 2 and 5, while the conversion of DPA to DHA requires an elongation to 24:5n−3 and desaturation to 24:6n−3 before peroxisomal beta-oxidation to yield DHA. As recently reviewed, ALA supplementation in humans generally leads to an increase in plasma EPA and DPA, but has little or no effect on DHA levels [1].
Previous studies have demonstrated a significant elevation in the level of DPA in the circulating lipid fractions when human subjects have received seal oil [2], [3], [4]. However, such effects cannot be directly attributed to the consumption of DPA since it represents approximately 5% of the fatty acids in seal oil with a higher level of EPA that has the potential to generate considerable amounts of DPA via chain elongation.
The previous knowledge on the metabolism of pure DPA in humans is limited to our study [5], where a supplementation of a total of 8 g of pure DPA or EPA revealed that within four days of supplementation, DPA and EPA demonstrated different and specific incorporation patterns into plasma lipid classes and red blood cell phospholipids.
In rats, short-term supplementation with pure DPA has significantly increased the concentration of DHA in liver and the concentration of EPA in the liver, heart and skeletal muscle, presumably by the process of retroconversion [6]. The retroconversion from DPA to EPA was especially apparent in the kidney of the rats [7]. The metabolism and the biological effects of DPA have been recently reviewed [8].
Tandem mass spectrometric lipidomic methods enable us to study the composition of lipids as they occur in the human plasma. This information is complimentary to the fatty acid composition that requires the cleavage of the fatty acids from the molecules in which they naturally occur. The lipidomic methods have previously revealed the non-steady state of lipids in the postprandial state [9], [10], [11].
We hypothesized that pure DPA and EPA would have different postprandial metabolic fates. To test this, a cross over study with healthy female volunteers and meals containing pure EPA and pure DPA was designed. A meal that contained olive oil was used as a control. Molecular level lipidomic analysis methods were used to investigate the structure and composition of the lipids. Special interest was placed on the metabolism of the n−3 PUFA in chylomicron triacylglycerols (TAG) and phospholipids.
Section snippets
Study design
Ten healthy normal weight females between the age of 20 to 30 took part in the randomized cross over study with three different breakfast meals. The subjects had a BMI between 20 to 25 kg/m2 and their habitual total consumption of omega-3 polyunsaturated fatty acids was not more than 0.5 g per day as assessed from a food frequency questionnaire [12], [13]. The baseline values for EPA and DHA proportions in their erythrocytes were 1.0±0.1 and 6.7±0.6 per cent (mean±standard error of mean),
Results
Chylomicron TAGs remained at almost fasting level after the DPA breakfast. The incremental area under the chylomicron TAG curve after the DPA meal was significantly reduced when compared with the corresponding area after the olive oil meal (p=0.021) or the area after the EPA meal (p=0.034). In plasma, there was no significant difference between the TAG areas under the curve after DPA meal and the olive oil control meal (p=0.078). Of the individual time points, the TAG concentration was lower
Discussion and conclusions
DPA is an elongated metabolite of EPA and it is one of the intermediate products between EPA and DHA. The present study investigated the postprandial metabolism of pure DPA and EPA in an olive oil containing meal.
The major finding in this study is that the addition of 2 g of DPA to the 18 g of olive oil almost completely eliminated the incorporation of fatty acids in chylomicrons within 5 h. In contrast, this effect was not seen with the addition of EPA.
One of the possible potential mechanisms
Acknowledgements
Dr Andrew Garnham is thanked for medical support and Dr Marissa Caldow for clinical trial support. Equateq Ltd (UK) is acknowledged for the generous provision of the pure supplements. Meat & Livestock Australia and Deakin University Strategic Research Centres for Molecular Medicine, and Chemistry and Biotechnology are acknowledged for their financial support. Osk. Huttunen Foundation and Finnish Food Research Foundation are acknowledged for support to Dr Linderborg. Finally we wish to
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