Metabolism of 18:4n-3 (stearidonic acid) and 20:4n-3 in salmonid cells in culture and inhibition of the production of prostaglandin F_2α(PGF_2α) from 20:4n-6 (arachidonic acid)

Abstract

Arachidonic acid (AA;) is the precursor of a range of highly biologically active derivatives, collectively termed eicosanoids, including prostaglandins, thromboxanes, leukotrienes and lipoxins, that act as autocrine hormones regulating many physiological processes including haemostasis, reproduction, immune and inflammatory responses. Eicosapentaenoic (EPA; 20:5n-3) and dihomo-γ-linolenic (20:3n-6) acids modulate eicosanoid metabolism by both inhibiting the conversion of AA to eicosanoids whilst simultaneously being converted to eicosanoids with different, often attenuated, properties compared to their AA homologues. Eicosatetraenoic acid (20:4n-3) is a naturally occurring C 20 polyunsaturated fatty acid (PUFA), present in fish oil at levels of around 1-2%, that has been suggested to be the active metabolite responsible for the anti-inflammatory effects of plant oils containing stearidonic acid (18:4n-3). However, the biochemical properties of 20:4n-3 in terms of cellular biology have rarely been investigated, partly due to difficulties in obtaining the fatty acid in high purity. In this paper, we describe methods for the medium scale laboratory preparation of high purity 20:4n-3, and investigate its metabolism in fish cell culture systems which normally contain significant amounts of n-3 PUFA. Thus the incorporation and metabolism of 18:4n-3 and 20:4n-3, and their distribution in phospholipid classes was studied in an

Fatty acid composition in chronic heart failure: low circulating levels of eicosatetraenoic acid and high levels of vaccenic acid are associated with disease severity and mortality

“…Moreover, as a precursor of EPA, it is possible that eicosatetraenoic acid could more accurately reflect n‐3 PUFA status than EPA. Furthermore, like EPA and other long‐chain n‐3 PUFAs, C20:4n‐3 has been shown to have anti‐inflammatory effects by inhibiting the conversion of arachidonic acid to prostaglandins [18]. Similarly, like other n‐3 PUFAs, C20:4n‐3 is readily incorporated into various phospholipid species, which is consistent with the possible modulatory effects on eicosanoid metabolism.…”

An alternative pathway for the effective production of the omega‐3 long‐chain polyunsaturates EPA and ETA in transgenic oilseeds

“…In the latter case, this was demonstrated by using verified biological standards previously generated in transgenic Arabidopsis lines accumulating juniperonic acid (Figure S1; Sayanova et al ., ). Interestingly, ETA is often observed at low levels in fish oils and has been ascribed anti‐inflammatory activities similar to EPA (Ghioni et al ., ). Thus, ETA can be considered as an additional omega‐3 LC‐PUFA widely distributed in marine food webs.…”

Effect of dietary echium oil on growth, fatty acid composition and metabolism, gill prostaglandin production and macrophage activity in Atlantic cod (Gadus morhua L.)

“…In earlier studies with fish cell cultures, supplemental STA was readily elongated to 20:4n‐3 (Ghioni et al 2004), suggesting that EO may be a useful oil to include in novel dietary formulations for marine fish as it has the potential to increase tissue levels of both 20:4n‐3 and 20:3n‐6. This could have beneficial effects in modulating ARA metabolism in fish, particularly when being fed VO diets with reduced levels of EPA that would normally regulate ARA and eicosanoid metabolism.…”

“…Another naturally occurring C 20 HUFA that can be converted to eicosanoids and modulate eicosanoid metabolism in mammals is 20:4n‐3 (Oliw, Sprecher & Hamberg 1986a,b; Careaga and Sprecher 1987; Croset, Bordet & Lagarde 1999). Recently we showed that 20:4n‐3 decreased the conversion of ARA into prostaglandins (PGs) in fish, as demonstrated by the decreased levels of PGF 2α produced in trout macrophages supplemented with 20:4n‐3 and ARA compared with cells supplemented with ARA alone (Ghioni, Porter, Taylor & Tocher 2004). In addition, 20:4n‐3 was converted into eicosanoids in fish cells as indicated by the presence of Δ 17,18 12‐HETE, Δ 17,18 PGE 1 and Δ 17,18 PGF 1α in extracts from rainbow trout ( Oncorhynchus mykiss ) macrophages incubated with 20:4n‐3 (Ghioni et al 2004).…”

“…Recently we showed that 20:4n‐3 decreased the conversion of ARA into prostaglandins (PGs) in fish, as demonstrated by the decreased levels of PGF 2α produced in trout macrophages supplemented with 20:4n‐3 and ARA compared with cells supplemented with ARA alone (Ghioni, Porter, Taylor & Tocher 2004). In addition, 20:4n‐3 was converted into eicosanoids in fish cells as indicated by the presence of Δ 17,18 12‐HETE, Δ 17,18 PGE 1 and Δ 17,18 PGF 1α in extracts from rainbow trout ( Oncorhynchus mykiss ) macrophages incubated with 20:4n‐3 (Ghioni et al 2004). However, there are few studies on 20:4n‐3 because of its rarity in natural oils with marine FOs being one of the few sources, although only in minor quantities around 1–2% of total fatty acids (Ackman 1980).…”