ReviewThe n-3 docosapentaenoic acid (DPA): A new player in the n-3 long chain polyunsaturated fatty acid family
Graphical abstract
Introduction
The n-3 long-chain polyunsaturated fatty acids (LCPUFA) have been widely studied and contribute to numerous beneficial effects, mainly associated with cardiovascular prevention [1], neurodevelopment, but also with the reduction of the risk of neurodegenerative diseases [2]. Indeed, these n-3 LCPUFA are involved in many processes such as the increase of membrane plasticity, the synthesis of oxygenated metabolites and the resolution of inflammation or the regulation of genes [3].
The majority of the n-3 LCPUFA studies were conducted using fish oils, composed of a mixture of three major n-3 LCPUFA: docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid (n-3 DPA). Most of the beneficial effects of fish oils have been attributed to DHA and then to EPA, for which there is growing interest in the independent and shared functions. On the other hand, the literature concerning the potential protective effects of n-3 DPA is brief because n-3 DPA represents less than one-third of each EPA and DHA in fish oils. In addition, n-3 DPA is not commercially available in sufficient quantity, with high purity (>98%) and at an affordable price to set up in vivo nutritional supplementation studies [4].
Studies about n-3 DPA have however begun to grow in recent years. n-3 DPA is indeed the second n-3 LCPUFA found in the brain (w/w), although its cerebral concentration is about 70 times lower than DHA. Moreover, the level of n-3 DPA in human milk is higher than that of EPA, similar to that of DHA and its level is more stable [5], implying a potential impact of n-3 DPA during pregnancy and development, which is the subject of a recent review [6]. While obtaining optimal tissue status in n-3 LCPUFA is one of the current public health challenges, n-3 DPA is also the only intermediate between EPA and DHA in the n-3 LCPUFA conversion pathway from α-linolenic acid (ALA) present in significant quantities in the diet. Therefore, could n-3 DPA serve as a dietary source or biological reservoir of DHA and EPA?
This paper reviews and summarizes the different knowledge about n-3 DPA and focus on the most recent findings synthesized in Table 1. To more thorough review concerning specific knowledges, the reader is encouraged to read another reviews specific about n-3 DPA or including it, as mentioned in adequate sections below [2,4,[6], [7], [8], [9], [10], [11], [12]].
Section snippets
Commercial availability
Suppliers who offer n-3 DPA> 98–99% purity cannot provide on demand enough quantities of n-3 DPA for in vivo studies at prices that are affordable for most research laboratories (supplier communications, 2017). Thus, studies focusing on n-3 DPA are often association studies in humans or in vitro studies. Most in vivo studies thus used n-3 DPA with a purity level <98% which therefore also contains mainly DHA, EPA and n-6 DPA, limiting the interpretation of these findings [8,9,13]. In addition,
A reservoir of EPA and DHA
n-3 DPA is the direct intermediate between EPA and DHA, in the conversion pathway from ALA, to be present in significant amounts in the human diet compared to the C24:5 n-3 and C24:6 n-3 derivatives [39]. This conversion pathway is well known and involves a sequence of desaturase enzymes adding one double bond to the carbon chain and elongase enzymes extending the carbon-chain of two carbons (Fig. 1). The n-3 LCPUFA conversion pathway is parallel to that of n-6 LCPUFA using the same sequence
Inflammation and cancer
The decrease in inflammation associated with n-3 DPA seems to come mainly from these lipid mediators, and mainly the specialized pro-resolving mediator (SPM) (maresins, protectins, resolvins). Indeed, incubation of human macrophages with Protectin D1n-3 DPA increased the monocyte differentiation, the phagocytic activity of macrophages and the apoptosis of neutrophils, which are key factors in the resolution of inflammation [71,76]. Moreover, the incubation of n-3 DPA-derived Maresin1n-3 DPA
Conclusion and prospects
An increasing number of association studies support the hypothesis that n-3 DPA is a bioactive fatty acid beneficial to human health. The suggested mechanisms involve the importance of n-3 DPA-derived lipid metabolites in the pro-resolution of inflammation in various models and mainly the importance of protectin D1 and resolvin D5 found in humans. Many other n-3 DPA-derived metabolites have also recently been identified and their potential physiological effects are not yet known. Likewise,
Declaration of interest
None.
Funding source
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Acknowledgments
We thank Pr. Thierry Durand (Institute of Biomolecules Max Mousseron, Montpellier, France) for the design of isoprostanes, Daniel Catheline (Laboratory of Biochemistry and Human Nutrition, Agrocampus Ouest, Rennes, France) for his help in the figure realization and Agrocampus Ouest, Rennes, France for funding.
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