- Review
- Open access
- Published:
The physiological and pathological properties of Mead acid, an endogenous multifunctional n-9 polyunsaturated fatty acid
Lipids in Health and Disease volume 22, Article number: 172 (2023)
Abstract
Mead acid (MA, 5,8,11-eicosatrienoic acid) is an n-9 polyunsaturated fatty acid (PUFA) and a marker of essential fatty acid deficiency, but nonetheless generally draws little attention. MA is distributed in various normal tissues and can be converted to several specific lipid mediators by lipoxygenase and cyclooxygenase. Recent pathological and epidemiological studies on MA raise the possibility of its effects on inflammation, cancer, dermatitis and cystic fibrosis, suggesting it is an endogenous multifunctional PUFA. This review summarizes the biosynthesis, presence, metabolism and physiological roles of MA and its relation to various diseases, as well as the significance of MA in PUFA metabolism.
Introduction
Mead acid (MA, 5,8,11-eicosatrienoic acid) is an n-9 polyunsaturated fatty acid (PUFA). MA was first identified by Mead and Slaton [1] in rats fed a fat-deficient diet and was determined to be derived from oleic acid [2]. Essential fatty acid (EFA) deficiency induces skin rash, alopecia, growth disorders and reproductive abnormalities [3, 4], accompanied by the appearance of MA in the blood. In EFA deficiency, MA derived from oleic acid appears to be synthesized rather than arachidonic acid (ARA) from linoleic acid (LA) (Fig. 1). MA is widely used as a marker of EFA deficiency; for example, the ratios of MA/ARA [5] and trienoic/tetraenoic acids are used to identify EFA deficiency [6,7,8]. Recent findings suggest that MA plays an important role as an endogenous PUFA, and that it is related to various diseases, such as inflammation, cancer, dermatitis and cystic fibrosis. Although these interesting studies have been reported individually, there has not yet existed a comprehensive overview of all available information about MA. The aim of this review is to provide an overview of the impact of MA in PUFA metabolism, the biosynthesis, presence and physiological roles of MA, and its relation to various diseases.
Biosynthesis and presence of MA
Most typical PUFAs belong to the n-6 or n-3 series and are derived from exogenous linoleic acid (LA) or α-linolenic acid (ALA), respectively. LA and ALA are converted physiologically to arachidonic acid (ARA) and eicosapentaenoic acid (EPA), respectively, by Δ6-desaturase, elongase and Δ5-desaturase. MA is synthesized from oleic acid (OA) in the n-9 series via the same enzyme system as for the n-6 and n-3 series, although Ichi et al. suggested another pathway via 20:1n-9 and 20:2n-9 [9].
MA has two distinct characteristics. First, MA is de novo synthesized from other carbon sources, such as acetate and sugars. MA is considered an endogenous PUFA, although all n-6 and n-3 PUFAs are derived from exogenous plant-derived PUFAs. Second, the amounts of MA and other n-9 PUFAs present in the body are small whereas ARA and EPA are abundant. Δ6-Desaturase, the rate-limiting enzyme in PUFA synthesis, has a much higher affinity for ALA and LA than for OA. Therefore, Δ6-desaturation of OA is highly suppressed in the presence of LA and ALA [10]. MA formation requires a marked decrease in both LA and ALA systemically or topically. Conversely, most tissues that synthesize ARA can potentially synthesize MA from endogenous OA.
MA is present systemically in EFA deficient animals, but is found in the plasma, blood vessels, liver, cartilage and eye lens of non-EFA-deficient animals. MA is also found in cultured cells and filamentous fungi [11,12,13,14,15,16,17,18,19,20] (Table 1). A small amount of MA is present in the major tissues of healthy adult humans, including in plasma (0.16%) [11], serum (0.24%) [13], blood vessels (0.1%) [15] and the liver (0.2%) [16]. Because MA is present at low concentrations, it is often overlooked, but this small amount of MA is distributed widely in various tissues. OA is an abundant fatty acid in various tissues and is a poor substrate for Δ6-desaturase. MA is found in muscle (1.42%) [14], spleen (0.2%) [16], brain (not quantified) [21], growth plate cartilage (4.67% and > 3%) [14, 22], cortical bone (0.36%) [14] and cord blood mononuclear cells from term (0.27%) and preterm (0.11%) [23], in addition to the tissues listed in Table 1.
Relatively large amounts of MA are detected in fetal tissues, including plasma (0.44%) [11], blood vessels (2.4%) [15] and the liver (0.4%) [16] (Table 1). Although ARA levels are much higher than those of MA in fetal tissues, LA is present at a low concentration of < 10%, which is less than one third the concentration in corresponding adult tissues, suggesting that fetuses are in a state of systemic and mild EFA deficiency. It supports that EFA intake by infants from breast milk or infant formula is necessary [24, 25]. For example, the MA content of fetal or infant cartilage is 2.0% (human), 3.0% (sheep) [16], 5.12% (calf) and 8.11% (pig), and is as high as 16.98% in 8–10 week-old chickens [14]. It is unclear why the MA concentration is so high in young cartilage but this may be due to cartilage being an avascular tissue, making it difficult to incorporate sufficient amounts of exogenous LA and ALA during development. The lens is another avascular tissue and contains 3.19% MA in near-term calves [14]. The effects of MA on angiogenesis are shown as described below. Aside from cartilage, a large amount of MA was found in the liver of rats fed a peroxisome proliferator-activated receptor (PPAR) α agonist (> 6% in the triacylglycerol fraction) [12], possibly due to the induction of desaturases and elongases by the PPARα agonist.
Importantly, cultured cells can contain considerable levels of MA (3.8% and 0.5%) [18, 19]. Several papers report quantifiable amounts of MA in cultured cells, and MA 8 be present in many cell cultures. Recently Okuno et al. used LC-MS/MS to show that the concentrations of polar lipids containing MA as acyl moiety increased in RAW 264.7 cells with increasing culture time, and that eicosanoid production was altered [26]. In pseudo-EFA deficiency, MA may tend to accumulate, for example, in rapidly growing cells whose capacity for EFA incorporation is low and for which the concentration of EFAs in the medium is limited. Potential EFA deficiency in cultured cells requires further study.
MA is also produced by filamentous fungi. A wild-type strain of the fungus Mortierella alpina produces an ARA-containing oil, and Δ12 desaturase-deficient mutants have been obtained [20]. These deficient strains synthesize MA (25.5%) instead of ARA (Table 1), similar to EFA-deficiency in mammals, and MA-containing oil accumulates in the cells [27, 28]. This MA-containing microbial oil is an alternative source of MA in addition to MA synthesized chemically [29, 30], and has been used in the pharmacological studies described below.
MA metabolism and its effects on the fatty acid profile
MA is detected in organisms with EFA-deficiency but EFA-deficient organisms are not always suitable for understanding the exact metabolism of MA and its effects on the fatty acid profile because the simultaneous drastic decrease in EFAs, such as ARA and docosahexaenoic acid (DHA), in such organisms makes it difficult to study MA metabolism.
This was addressed by administering exogenous MA to rats or mice, for 3 to 8 weeks, which increased the MA concentration in the plasma, liver, spleen, peritoneal exudate cells [31,32,33,34], transplanted human breast cancer cells [35], mammary tissue [36], lens and retina [37]. A dose-dependent increase of MA was observed in the plasma, liver, spleen and peritoneal exudate cells [31] in which the percentage of MA in fatty acids was above 20% [31, 33, 35,36,37]. These results suggest that MA can be absorbed from the digestive tract and transferred to various tissues efficiently. MA was detected as acyl moiety of phospholipids, triglycerides and cholesterol esters in plasma [31], and that of phospholipids in the liver, spleen and peritoneal exudate cells [31,32,33]. In peritoneal exudate cells, MA was contained in phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol [33]. These findings suggest that the absorption and distribution of MA is widespread physiologically and is similar to that of other C20 PUFAs, such as ARA and EPA.
Most of the studies described above also detected docosatrienoic acid (DTA, 22:3 n-9), believed to be formed by the elongation of MA, similar to the C20 analogues, ARA and EPA. The DTA concentration was around 3–7% and was almost half that of MA in spleen and peritoneal exudate cells [31, 33, 34]. The presence of the further metabolites, tetracosatrienoic acid (24:3 n-9), tetracosatetraenoic acid (24:4 n-9) and docosatetraenoic acid (22:4 n-9), was not detected, although the homologous metabolites in the n-6 and n-3 series were well known, with docosapentaenoic acid (22:5 n-6) and DHA formed, respectively [38]. Metabolism through the C24 fatty acids of the n-9 series may be impeded, apart from the n-6 and n-3 series.
The above studies showed that the concentrations of other PUFAs, such as ARA, EPA and DHA, decreased due to their partial displacement by MA. The results suggest that MA competes with other long chain PUFAs in PUFA metabolism, and that the presence of MA is not solely due to the decrease in ARA in patients with EFA deficiency. The competition of MA with other PUFAs, especially ARA, is a main mechanism underlying its various physiological and pathological activities, as described below.
Careful attention is needed for estimating the effects of MA on the increase in MA concentration or the displacement of other PUFAs in tissues. In most cases, large amounts of fatty acids other than MA are contained in MA-containing oil itself [20, 27, 28] or as ingredients of diet or culture medium, and may interact with the effects of MA.
Conversion of MA to lipid mediators
MA is now recognized to also be converted to various lipid mediators similar to those of from ARA (Fig. 2). We here review the current knowledge and explore avenues for further research into the roles of MA-derived lipid mediators in cardiovascular biology, carcinogenesis and many inflammatory diseases [39,40,41]. This conversion is due to MA having a structure similar to that of ARA and having identical double bonds at the 5, 8 and 11 positions. The properties of most of lipid mediators derived from MA remain unclear but may be related to the physiological and pharmacological activities of MA. It should, incidentally, be noted that it is important to distinguish MA from another eicosatrienoic acid, dihomo-γ-linolenic acid (DGLA), which has double bonds at the 8, 11 and 14 positions and is an n-6 PUFA (Fig. 1). DGLA has various unique activities and is metabolized to specific lipid mediators that differ from MA-derived mediators [42,43,44].
5-Lipoxygenase (LOX)
Leukotriene (LT) is a major 5-LOX metabolite. LT derived from ARA is categorized as 4-series [41]. 5-LOX converts ARA to 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and then to LTA4. LTA4 is conjugated with glutathione to form LTC4, which is sequentially converted to LTD4 and then LTE4. LTA4 can be also converted to LTB4 by LTA4 hydrolase. 5-HPETE can be converted to 5-hydroxyeicosatetraenoic acid (5-HETE) and 5-oxo-eicosatetraenoic acid (5-oxo-ETE).
Of the MA-derived lipid mediators, the 5-LOX metabolites have been the most intensively studied since the 1980s. Most ARA-derived 5-LOX metabolite analogues are formed from MA, i.e., the 3-series LT. Mouse mastocytoma cells were found to convert MA to LTC3 and LTD3 [45]. The distribution [46] and metabolism [47] of LTC3, and the conversion of LTD3 to LTE3 [48], were reported successively. LTA3 is a poor substrate for human neutrophil LTA4 hydrolase and a potent inhibitor of this enzyme [49], which may cause reduction of LTB4 as described below. A tyrosine residue (Y383) of LTA4 hydrolase attacks the conjugated triene epoxide of LTA3, resulting in the covalent attachment of LTA3 to LTA4 hydrolase [50].
LTB3 has been found in cultured cells [26], despite the fact that LTA3 inhibits LTA4 hydrolase as described above. LTB3 can displace [3 H]-LTB4 from both rat and human leukocyte membranes with the following affinity: LTB4 = LTB3 > LTB5 [51]. 5-oxo-ETE is a potent chemoattractant for neutrophils and eosinophils formed from ARA, and its actions are mediated by the oxoeicosanoid receptor. Similarly, 5-oxo-ETrE is formed from MA, and activates granulocytes with a potency similar to 5-oxo-ETE [52].
Lipoxins (LX) are pro-resolving lipid mediators formed from ARA by 5-LOX and 12/15-LOX [53]. Because MA lacks a Δ15 double bond, no LX-type mediators are likely formed from MA. LXA4 and LXB4 are produced upon incubating LTA4 with human platelets, but not upon incubation with LTA3 [54].
12/15-LOX
12/15-LOX converts ARA into 8-HETE, 11-HETE, 12-HETE and 15-HETE [55, 56], and thus the corresponding HETrEs might be generated from MA. The HETrE 12-hydroxy-5,8,10-eicosatrienoic acid (12-HETrE) is formed from MA in human platelets [57] and exhibits prostaglandin (PG) E2-like biphasic effects on platelet aggregation. Other MA-derived HETrEs are likely catalyzed by 12/15-LOX but have not been reported.
Cyclooxygenase (COX)
COX converts ARA into PGH2, which has a characteristic five-membered ring, and then is metabolized further to various prostanoids. However, COX converts MA into several metabolites lacking a five-membered ring, and especially into 13-hydroxy-5,8,11-eicosatrienoic acid (13-HETrE) [58, 59]. 11-Hydroxy-5,8,12-eicosatrienoic acid (11-HETrE) and 9-hydroxy-5,7,11-eicosatrienoic acid (9-HETrE) are minor metabolites. COX-2, an inducible type of COX, also converts MA to 13-HETrE and 11-HETrE [60]. These HETrEs are formed by COX, not by LOX, but the conversion of MA by COX is slow compared with the conversion of ARA [60, 61]. In addition to these HETrEs, 8,11-dihydroxy-5,9,12-eicosatrienoic acid from MA was reported [58].
Mead ethanolamide and glycerol 2-MA
Arachidonoylethanolamide and 2-arachidonoylglycerol (2-AG) are endogenous agonists of cannabinoid CB1 and CB2 receptors [62]. Mead ethanolamide is biosynthesized from MA in rat and human hippocampal membranes as efficiently as arachidonoylethanolamide is synthesized from ARA [63]. Chemically synthesized mead ethanolamide is equipotent to arachidonoylethanolamide as a competitor of the cannabinoid agonist CP55,940, and it binds to plasma membranes expressing the human CB1 receptor [63].
A principal pathway to 2-AG is the degradation of 2-arachidonoyl phospholipids to 2-arachidonoyl-diacylglycerol by phospholipase C, followed by deacylation to 2-AG by an sn-1-specific diacylglycerol lipase [63]. Phosphatidylinositol [26, 64] and phosphatidylcholine [64] containing MA were detected, with the other acyl moiety generally being saturated fatty acid [26, 64]. Because unsaturated fatty acids are preferentially combined with the sn-2-position of phospholipids and diacylglycerol, the diacylglycerol is likely derivatized by MA at the sn-2-position, in which case glycerol 2-MA would be formed. This compound was recently detected in human plasma [65]. It is unknown whether the bioactivity of glycerol 2-MA is similar to that of 2-AG.
Relation of MA to Diseases
MA is synthesized endogenously, is distributed widely, is a competitor of other PUFAs and is converted to various unique lipid mediators in the body, all of which suggest the physiological and pathological importance of MA. MA metabolism and the activities of MA-derived mediators appear intertwined with ARA metabolism and the systemic regulation of ARA. The relation of MA to various diseases is described below.
Inflammation
Many lipid mediators are involved in inflammation and repair. The relation between MA and general inflammation was among the first to be investigated. Dietary supplementation of male Wistar rats with MA increased the concentration of MA in neutrophils and inhibited A23187-stimulated LTB4 synthesis in these cells, but did not inhibit the synthesis of two other products of 5-LOX metabolism, 5-HETE and the all-trans isomers of LTB4 [32, 66]. The authors of that study therefore considered that the effects of MA supplementation resulted from the inhibition of LTA hydrolase. Leukotriene B4 synthesis was inhibited in neutrophils from patients with EFA deficiency, and an in vitro experiment suggested that MA is a more potent inhibitor than EPA [67]. Dietary supplementation with MA also increased the content of MA in the phospholipids of peritoneal exudate cells in mice and suppressed the generation of platelet-activating factor in peritoneal cells stimulated by zymosan. The suppression effect of MA was comparable to that of DHA [33]. That study showed that MA supplementation attenuates liver injury induced by galactosamine/lipopolysaccharide in mice. The synthesis of LTB4 and LTE4 in peritoneal cells was suppressed in MA-fed mice whereas that of PGE2 or 6-keto PGE1α was not [34]. These results suggest that MA may inhibit the 5-LOX pathway but not the COX pathway in vivo. However, as described above, the concentration of MA increased in RAW 264.7 cells with increasing culture time and the production of PGD2, PGE2 and TXA2 decreased as LTC4 and LTB4 decreased [26]. Further studies are needed to clarify the effects of MA on the COX pathway and on the total inflammation phenotype.
Cancer
An apparent correlation between cancer and PUFAs, and especially between cancer and n-3 PUFAs in fish, has been actively studied. The World Cancer Research Fund reviewed various cancer risks in 2018 and concluded that there is limited evidence suggesting that consumption of fish decreases the risk of liver cancer and colorectal cancer [68]. Many lipid mediators are involved in the process of cancer, leading to studies on the relation between MA and cancer.
Carcinogenesis is believed to be a sequential multistep process, i.e., DNA damage (initiation phase), enhanced cell proliferation (promotion phase), and metastasis (progression phase). MA inhibits expression of the cell-cell adhesion molecule, E-cadherin, in human squamous cell carcinoma in vitro, affecting metastasis [69]. Another study indicated that MA affects E-cadherin expression and cell proliferation differently, depending on the cell-line (urothelium T-24, breast MCF-7 and colon HRT-18 cells) [21]. Angiogenesis is important for cancer proliferation and metastasis. The content of MA is high in avascular cartilage, as described above, leading to studies on the effect of MA on angiogenesis. Angiogenesis is inhibited by the addition of MA to human umbilical vein endothelial cells [70]. Pathological angiogenesis was recently reported to promote MA accumulation in the retina [71].
The most advanced studies have been conducted on breast cancer. MA suppresses mammary cancers by suppressing cell proliferation, but does not accelerate cell death. MA administration inhibits the growth of KPL-1 human breast cancer cells in vitro and in vivo [35]. The levels of vascular endothelial growth factor receptor (VEGFR) 1 and VEGFR2 decrease upon treatment with MA. VEGF, VEGFR1 and VEGFR2 expression co-localize in KPL-1 cells, indicating that cell growth suppression involves VEGF signaling directly to KPL-1 cells by an autocrine process, although MA apparently does not influence angiogenesis.
The initiation and promotion phases of mammary carcinogenesis in N-methyl-N-nitrosourea-induced cancer model in rats were also suppressed upon the administration of MA [36]. On the other hand, MA administration did not suppress 7,12‑dimethylbenz[a]anthracene‑induced breast cancer in rats [72]. Different results depending on the carcinogens were reported. With regard to epidemiological data, a nested case-control study reported that the MA composition in plasma total lipids was inversely associated with overall cancer risk and breast cancer risk [73]. Beneficial outcomes following the consumption of omega-9 fatty acids, including MA, for cancer management have been reviewed [74].
Dermatitis
Dermatitis is a typical symptom of EFA deficiency [3, 4] and thus the relation between MA and dermatitis has attracted attention. Topical application of MA to the skin of hairless mice causes scaly dermatitis with hyperplasia [75], which formerly led to MA being considered a cause of dermatitis. However, it was recently shown that the abnormality in the epidermal permeability barrier in patients with EFA deficiency is due to the replacement of linoleic acid with oleic acid in O-acylsphingolipids [76], suggesting that MA may not necessarily be an exacerbating factor. It was recently reported that dietary coconut oil ameliorated skin contact hypersensitivity through MA production in mice [77]. Intraperitoneal injection of MA inhibits contact hypersensitivity and reduces the number of neutrophils infiltrating the skin, and inhibits the directional migration of neutrophils by inhibiting filamentous actin polymerization and leukotriene B4 production. MA inhibits retinol-induced irritant contact dermatitis via PPARα [78], inhibits p38 mitogen-activated protein kinase phosphorylation and prevents both keratinocyte hyperproliferation and the gene expression of neutrophil chemoattractants.
Cystic fibrosis (CF)
CF is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator gene, which encodes a chloride and bicarbonate channel expressed in the apical membrane of epithelial cells and affects pulmonary, endocrine, gastrointestinal, pancreatic, biliary and reproductive systems [79]. These mutations are believed to have no direct relation to fatty acid metabolism, but defective essential fatty acid metabolism is observed in patients with CF [80]. An increased content of MA and a decrease in EFAs, such as LA, ALA, ARA and DHA, has been observed in the serum of CF patients [81,82,83]. However, these fatty acid profiles differ from those of typical EFA deficiency, indicating that LA and ALA are slightly decreased but still adequate compared with EFA deficiency. Genotype and sex may have some correlation with EFA status in CF patients [84]. An attempt to reduce morbidity and mortality in CF patients involved 23 randomized controlled trials to compare omega-3 fatty acid supplements with placebo and showed limited benefits with relatively few adverse effects [85].
Other diseases
MA is incorporated into platelets [86] and endothelial cells [87]. MA increases the response of platelets to all aggregation agents studied when added simultaneously with the agent [88]. MA suppresses osteoblastic activity in the mouse osteoblast cell line MC3T3-E1 and in goldfish scales [89] and was not associated with risk of posterior longitudinal ligament ossification in a case-control study [90]. Beneficial effects of MA on experimental bowel lesions have been reported [91]. The MA content is low in the serum of phenylketonuria patients [13], and high in the phospholipids in the cerebral cortex of Reelin-deficient mice [21].
However, MA supplementation does not rescue rats from cataract and retinal degeneration induced by N-methyl-N-nitrosourea [37]. Higher plasma MA levels are associated with fibrosis stage 3–4 of nonalcoholic fatty liver disease [92].
The strength of this study lies in its comprehensive review of MA on biosynthesis, presence, metabolism and physiological and pathological roles. While previous studies have reviewed passive MA formation in response to EFA deficiency, the present review emphasizes the active roles of MA and presents a thorough collection of studies on MA-derived lipid mediators from the 1980s to the present day.
The limitation of this study is its narrative approach, which may cause oversights or biases. Furthermore, the discussion of pathological roles is not entirely satisfactory due to the limited number of supporting studies available. However, inflammatory diseases, cancers, and dermatitis, as demonstrated here, are intensively influenced by lipid mediators, such as PG and LT, which act as both causative and regulatory factors. Recent research developments regarding the impact of MA on these conditions encourage a greater understanding of its potential contributions to therapy. Further studies are needed to explore the pathological roles of MA.
Conclusion
This review summarizes the biosynthesis, presence, metabolism and physiological roles of MA, and its role in various diseases. MA is synthesized de novo in the body and is present not only in conditions of EFA deficiency but also in major normal tissues. An increasing number of studies have reported the relation between MA and diseases, such as inflammation, cancer, dermatitis and cystic fibrosis, and epidemiological data have been reported recently.
Future perspective
It is expected that further studies directed towards understanding the role of MA, especially to address two points. The first is to clarify the extensive presence of MA physiologically. As described in this review, MA can be synthesized due to topical or temporal EFA deficiency, such as in avascular tissues, even in an EFA-sufficient status. The widespread distribution of MA in tissues will be established soon using new high-resolution techniques. MA is often produced in cultured cells, depending on the experimental conditions. Because it has various unique properties, it is important to determine the fatty acid profile of cultured cells.
The second point is to conduct studies on MA-derived lipid mediators. About forty years ago, MA attracted attention as a natural ARA analogue and was studied extensively but this information is inadequate and out of date. An unknown MA-derived lipid mediator or physiological role perhaps remains to be discovered. MA is an endogenous PUFA, and its various functions may result from MA-derived lipid mediators.
MA tends to be overlooked compared to other n-6 or n-3 PUFAs, but it is widely distributed in tissues and may have various physiological and pathological roles. Further studies on MA will likely improve our understanding of fatty acid metabolism.
Data Availability
Not applicable.
Abbreviations
- ALA:
-
α-linolenic acid
- ARA:
-
Arachidonic acid
- CF:
-
Cystic fibrosis
- COX:
-
Cyclooxygenase
- DGLA:
-
Dihomo-γ-linolenic acid
- DHA:
-
Docosahexaenoic acid
- DTA:
-
Docosatrienoic acid
- EFA:
-
Essential fatty acid
- EPA:
-
Eicosapentaenoic acid
- HETE:
-
Hydroxyeicosatetraenoic acid
- HETrE:
-
Hydroxyeicosatrienoic acid
- HPETE:
-
Hydroperoxyeicosatetraenoic acid
- LA:
-
Linoleic acid
- LOX:
-
Lipoxygenase
- LT:
-
Leukotriene
- LX:
-
Lipoxins
- 5-oxo-ETE:
-
5-oxo-eicosatetraenoic acid
- OA:
-
Oleic acid
- MA:
-
Mead acid
- PG:
-
Prostaglandin
- PPAR:
-
Peroxisome proliferator-activated receptor
- PUFA:
-
Polyunsaturated fatty acids
- VEGF:
-
Vascular endothelial growth factor
References
Mead JF, Slaton WH. Metabolism of essential fatty acids. III. Isolation of 5,8,11-eicosatrienoic acid from fat-deficient rats. J Biol Chem. 1956;219(2):705–9. https://doi.org/10.1016/S0021-9258(18)65729-1.
Fulco AJ, Mead JF. Metabolism of essential fatty acids. VIII. Origin of 5,8,11-eicosatrienoic acid in the fat-deficient rat. J Biol Chem. 1959;234(6):1411–6. https://doi.org/10.1016/S0021-9258(18)70021-5.
Barr LH, Dunn GD, Brennan MF. Essential fatty acid deficiency during total parenteral nutrition. Ann Surg. 1981;193(3):304–11. https://doi.org/10.1097/00000658-198103000-00009.
Innis SM. Essential fatty acids in growth and development. Prog Lipid Res. 1991;30(1):39–103. https://doi.org/10.1016/0163-7827(91)90006-q.
Siguel EN, Chee KM, Gong JX, Schaefer EJ. Criteria for essential fatty acid deficiency in plasma as assessed by capillary column gas-liquid chromatography. Clin Chem. 1987;33(10):1869–73. https://doi.org/10.1093/clinchem/33.10.1869.
Holman RT. The ratio of trienoic:tetraenoic acids in tissue lipids as a measure of essential fatty acid requirement. J Nutr. 1960;70:405–10. https://doi.org/10.1093/jn/70.3.405.
Lamptey MS, Walker BL. Learning behavior and brain lipid composition in rats subjected to essential fatty acid deficiency during gestation, lactation and growth. J Nutr. 1978;108(3):358–67. https://doi.org/10.1093/jn/108.3.358.
Collins FD, Sinclair AJ, Royle JP, Coats DA, Maynard AT, et al. Plasma lipids in human linoleic acid deficiency. Nutr Metab. 1971;13(3):150–67. https://doi.org/10.1159/000175332.
Ichi I, Kono N, Arita Y, Haga S, Arisawa K, Yamano M, et al. Identification of genes and pathways involved in the synthesis of Mead acid (20:3n-9), an indicator of essential fatty acid deficiency. Biochim Biophys Acta. 2014;1841(1):204–13. https://doi.org/10.1016/j.bbalip.2013.10.013.
Brenner RR, Peluffo RO. Effect of saturated and unsaturated fatty acids on the desaturation in vitro of palmitic, stearic, oleic, linoleic, and linolenic acids. J Biol Chem. 1966;241(22):5213–9. https://doi.org/10.1016/S0021-9258(18)96419-7.
van Houwelingen AC, Sørensen JD, Hornstra G, Simonis MM, Boris J, Olsen SF, et al. Essential fatty acid status in neonates after fish-oil supplementation during late pregnancy. Br J Nutr. 1995;74(5):723–31. https://doi.org/10.1079/bjn19950175.
Wang Y, Botolin D, Christian B, Busik J, Xu J, Jump DB. Tissue-specific, nutritional, and developmental regulation of rat fatty acid elongases. J Lipid Res. 2005;46(4):706–15. https://doi.org/10.1194/jlr.m400335-jlr200.
Drzymała-Czyż S, Kałużny Ł, Krzyżanowska-Jankowska P, Walkowiak D, Mozrzymas R, Walkowiak J. Deficiency of long-chain polyunsaturated fatty acids in phenylketonuria: a cross-sectional study. Acta Biochim Pol. 2018;65(2):303–8. https://doi.org/10.18388/abp.2018_2565.
Adkisson HD 4th, Risener FS Jr, Zarrinkar PP, Walla MD, Christie WW, Wuthier RE. Unique fatty acid composition of normal cartilage: discovery of high levels of n-9 eicosatrienoic acid and low levels of n-6 polyunsaturated fatty acids. FASEB J. 1991;5(3):344–53. https://doi.org/10.1096/fasebj.5.3.2001795.
Hornstra G, van Houwelingen AC, Simonis M, Gerrard JM. Fatty acid composition of umbilical arteries and veins: possible implications for the fetal EFA-status. Lipids. 1989;24(6):511–7. https://doi.org/10.1007/bf02535131.
Cleland KA, James MJ, Neumann MA, Gibson RA, Cleland LG. Differences in fatty acid composition of immature and mature articular cartilage in humans and sheep. Lipids. 1995;30(10):949–53. https://doi.org/10.1007/bf02537487.
Rodriguez A, Sarda P, Nessmann C, Boulot P, Leger CL, Descomps B. Delta6- and delta5-desaturase activities in the human fetal liver: kinetic aspects. J Lipid Res. 1998;39(9):1825–32. https://doi.org/10.1016/S0022-2275(20)32170-2.
Msika O, Brand A, Crawford MA, Yavin E. NGF blocks polyunsaturated fatty acids biosynthesis in n-3 fatty acid-supplemented PC12 cells. Biochim Biophys Acta. 2012;1821(7):1022–30. https://doi.org/10.1016/j.bbalip.2012.04.007.
Heyd VL, Eynard AR. Effects of eicosatrienoic acid (20:3 n-9, Mead’s acid) on some promalignant-related properties of three human cancer cell lines. Prostaglandins Other Lipid Mediat. 2003;71(3–4):177–88. https://doi.org/10.1016/s1098-8823(03)00037-6.
Kawashima H, Nishihara M, Hirano Y, Kamada N, Akimoto K, Konishi K, et al. Production of 5,8,11-Eicosatrienoic Acid (Mead Acid) by a (Delta)6 desaturation activity-enhanced mutant derived from a (Delta)12 desaturase-defective mutant of an arachidonic acid-producing Fungus, Mortierella alpina 1S-4. Appl Environ Microbiol. 1997;63(5):1820–5. https://doi.org/10.1128/aem.63.5.1820-1825.1997.
Mizukami T, Ikeda K, Shimanaka Y, Korogi K, Zhou C, Takase H, et al. Reelin deficiency leads to aberrant lipid composition in mouse brain. Biochem Biophys Res Commun. 2018;505(1):81–6. https://doi.org/10.1016/j.bbrc.2018.09.089.
Xu H, Watkins BA, Adkisson HD. Dietary lipids modify the fatty acid composition of cartilage, isolated chondrocytes and matrix vesicles. Lipids. 1994;29(9):619–25. https://doi.org/10.1007/bf02536096.
Crawford MA, Sinclair AJ, Hall B, Ogundipe E, Wang Y, et al. The imperative of arachidonic acid in early human development. Prog Lipid Res. 2023;91:101222. https://doi.org/10.1016/j.plipres.2023.101222.
Salem N Jr, Van Dael P. Arachidonic acid in human milk. Nutrients. 2020;12(3):626. https://doi.org/10.3390/nu12030626.
Rajion MA, McLean JG, Cahill RN. Essential fatty acids in the fetal and newborn lamb. Aust J Biol Sci. 1985;38(1):33–40.
Okuno T, Gijón MA, Zarini S, Martin SA, Barkley RM, Johnson CA, et al. Altered eicosanoid production and phospholipid remodeling during cell culture. J Lipid Res. 2018;59(3):542–49. https://doi.org/10.1194/jlr.m083030.
Sakuradani E, Kamada N, Hirano Y, Nishihara M, Kawashima H, Akimoto K, et al. Production of 5,8,11-eicosatrienoic acid by a delta5 and delta6 desaturation activity-enhanced mutant derived from a delta12 desaturation activity-defective mutant of Mortierella alpina 1S-4. Appl Microbiol Biotechnol. 2002;60(3):281–7. https://doi.org/10.1007/s00253-002-1128-z.
Sakuradani E, Ando A, Ogawa J, Shimizu S. Improved production of various polyunsaturated fatty acids through filamentous fungus Mortierella alpina breeding. Appl Microbiol Biotechnol. 2009;84(1):1–10. https://doi.org/10.1007/s00253-009-2076-7.
Ghosh A, Koley M, Dutta J. Preparation of cis, cis, cis-5,8,11-eicosatrienoic acid from arachidonic acid. Lipids. 1982;17(4):314–6. https://doi.org/10.1007/bf02534947.
Parish HA, Gilliom RD, Purcell WP. A simple synthesis of 5,8,11-eicosatrienoic acid. Lipids. 1983;18(12):894–5. https://doi.org/10.1007/BF02534568.
Cleland LG, Neumann MA, Gibson RA, Hamazaki T, Akimoto K, James MJ. Effect of dietary n-9 eicosatrienoic acid on the fatty acid composition of plasma lipid fractions and tissue phospholipids. Lipids. 1996;31(8):829–37. https://doi.org/10.1007/bf02522978.
James MJ, Gibson RA, Neumann MA, Cleland LG. Effect of dietary supplementation with n-9 eicosatrienoic acid on leukotriene B4 synthesis in rats: a novel approach to inhibition of eicosanoid synthesis. J Exp Med. 1993;178(6):2261–5. https://doi.org/10.1084/jem.178.6.2261.
Watanabe S, Doshi M, Akimoto K, Kiso Y, Hamazaki T. Suppression of platelet-activating factor generation and modulation of arachidonate metabolism by dietary enrichment with (n-9) eicosatrienoic acid or docosahexaenoic acid in mouse peritoneal cells. Prostaglandins Other Lipid Mediat. 2001;66(2):109–20. https://doi.org/10.1016/s0090-6980(01)00152-6.
Doshi M, Watanabe S, Niimoto T, Kawashima H, Ishikura Y, Kiso Y, Hamazaki T. Effect of dietary enrichment with n-3 polyunsaturated fatty acids (PUFA) or n-9 PUFA on arachidonate metabolism in vivo and experimentally induced inflammation in mice. Biol Pharm Bull. 2004;27(3):319–23. https://doi.org/10.1248/bpb.27.319.
Kinoshita Y, Yoshizawa K, Hamazaki K, Emoto Y, Yuri T, Yuki M, et al. Mead acid inhibits the growth of KPL-1 human Breast cancer cells in vitro and in vivo. Oncol Rep. 2014;32(4):1385–94. https://doi.org/10.3892/or.2014.3390.
Kinoshita Y, Yoshizawa K, Hamazaki K, Emoto Y, Yuri T, Yuki M, et al. Dietary effects of mead acid on N-methyl-N-nitrosourea-induced mammary cancers in female Sprague-Dawley rats. Biomed Rep. 2016;4(1):33–9. https://doi.org/10.3892/br.2015.530.
Emoto Y, Yoshizawa K, Hamazaki K, Kinoshita Y, Yuki M, Yuri T, et al. Mead acid supplementation does not rescue rats from cataract and retinal degeneration induced by N-methyl-N-nitrosourea. J Toxicol Pathol. 2015;28(1):11–20. https://doi.org/10.1293/tox.2014-0036.
Sprecher H. Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim Biophys Acta. 2000;1486(2–3):219–31. https://doi.org/10.1016/s1388-1981(00)00077-9.
Nakamura M, Shimizu T. Recent advances in function and structure of two leukotriene B4 receptors: BLT1 and BLT2. Biochem Pharmacol. 2022;203:115178. https://doi.org/10.1016/j.bcp.2022.115178.
Sakai M, Kakutani S, Horikawa C, Tokuda H, Kawashima H, Shibata H, et al. Arachidonic acid and cancer risk: a systematic review of observational studies. BMC Cancer. 2012;12:606. https://doi.org/10.1186/1471-2407-12-606.
Miyata J, Fukunaga K, Kawashima Y, Ohara O, Kawana A, Asano K, et al. Dysregulated metabolism of polyunsaturated fatty acids in eosinophilic allergic Diseases. Prostaglandins Other Lipid Mediat. 2020;150:106477. https://doi.org/10.1016/j.prostaglandins.2020.106477.
Kawashima H, Tateishi N, Shiraishi A, Teraoka N, Tanaka T, Tanaka A, et al. Oral administration of dihomo-gamma-linolenic acid prevents development of atopic dermatitis in NC/Nga mice. Lipids. 2008;43(1):37–43. https://doi.org/10.1007/s11745-007-3129-2.
Amagai Y, Oida K, Matsuda A, Jung K, Kakutani S, Tanaka T, et al. Dihomo-γ-linolenic acid prevents the development of atopic dermatitis through prostaglandin D1 production in NC/Tnd mice. J Dermatol Sci. 2015;79(1):30–7. https://doi.org/10.1016/j.jdermsci.2015.03.010.
Tanaka T, Kakutani S, Horikawa C, Kawashima H, Kiso Y. Oral supplementation with dihomo-γ-linolenic acid (DGLA)-enriched oil increases serum DGLA content in healthy adults. Lipids. 2012;47(6):643–6. https://doi.org/10.1007/s11745-012-3664-3.
Hammarström S. Conversion of 5,8,11-eicosatrienoic acid to leukotrienes C3 and D3. J Biol Chem. 1981;256(5):2275–9. https://doi.org/10.1016/S0021-9258(19)69773-5.
Appelgren LE, Hammarström S. Distribution and metabolism of 3H-labeled leukotriene C3 in the mouse. J Biol Chem. 1982;257(1):531–5. https://doi.org/10.1016/S0021-9258(19)68396-1.
Hammarström S. Metabolism of leukotriene C3 in the guinea pig. Identification of metabolites formed by lung, liver, and kidney. J Biol Chem. 1981;256(18):9573–8. https://doi.org/10.1016/S0021-9258(19)68396-1.
Bernström K, Hammarström S. Metabolism of leukotriene D by porcine kidney. J Biol Chem. 1981;256(18):9579–82. https://doi.org/10.1016/S0021-9258(19)68801-0.
Evans JF, Nathaniel DJ, Zamboni RJ, Ford-Hutchinson AW. Leukotriene A3. A poor substrate but a potent inhibitor of rat and human neutrophil leukotriene A4 hydrolase. J Biol Chem. 1985;260(20):10966–70. https://doi.org/10.1016/S0021-9258(17)39131-7.
Mancini JA, Waugh RJ, Thompson JA, Evans JF, Belley M, Zamboni R, et al. Structural characterization of the covalent attachment of leukotriene A3 to leukotriene A4 hydrolase. Arch Biochem Biophys. 1998;354(1):117–24. https://doi.org/10.1006/abbi.1998.0670.
Charleson S, Evans JF, Zamboni RJ, Leblanc Y, Fitzsimmons BJ, Leveillé C, et al. Leukotriene B3, leukotriene B4 and leukotriene B5; binding to leukotriene B4 receptors on rat and human leukocyte membranes. Prostaglandins. 1986;32(4):503–16. https://doi.org/10.1016/0090-6980(86)90033-x.
Patel P, Cossette C, Anumolu JR, Gravel S, Lesimple A, Mamer OA, et al. Structural requirements for activation of the 5-oxo-6E,8Z, 11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) receptor: identification of a mead acid metabolite with potent agonist activity. J Pharmacol Exp Ther. 2008;325(2):698–707. https://doi.org/10.1124/jpet.107.134908.
Chiang N, Arita M, Serhan CN. Anti-inflammatory circuitry: lipoxin, aspirin-triggered lipoxins and their receptor ALX. Prostaglandins Leukot Essent Fatty Acids. 2005;73(3–4):163–77. https://doi.org/10.1016/j.plefa.2005.05.003.
Romano M, Serhan CN. Lipoxin generation by permeabilized human platelets. Biochemistry. 1992;31(35):8269–77. https://doi.org/10.1021/bi00150a021.
Kiss L, Schütte H, Mayer K, Grimm H, Padberg W, Seeger W, et al. Synthesis of arachidonic acid-derived lipoxygenase and cytochrome P450 products in the intact human lung vasculature. Am J Respir Crit Care Med. 2000;161(6):1917–23. https://doi.org/10.1164/ajrccm.161.6.9906058.
Klawitter J, Klawitter J, McFann K, Pennington AT, Abebe KZ, Brosnahan G, et al. Bioactive lipid mediators in polycystic Kidney Disease. J Lipid Res. 2014;55(6):1139–49. https://doi.org/10.1194/jlr.p042176.
Lagarde M, Burtin M, Rigaud M, Sprecher H, Dechavanne M, Renaud S. Prostaglandin E2-like activity of 20:3n-9 platelet lipoxygenase end-product. Lagarde FEBS Lett. 1985;181(1):53–6. https://doi.org/10.1016/0014-5793(85)81112-1.
Elliott WJ, Morrison AR, Sprecher H, Needleman P. Calcium-dependent oxidation of 5,8,11-icosatrienoic acid by the cyclooxygenase enzyme system. J Biol Chem. 1986;261(15):6719–24. https://doi.org/10.1016/S0021-9258(19)62675-X.
Oliw EH, Hörnsten L, Sprecher H, Hamberg M. Oxygenation of 5,8,11-eicosatrienoic acid by prostaglandin endoperoxide synthase and by cytochrome P450 monooxygenase: structure and mechanism of formation of major metabolites. Arch Biochem Biophys. 1993;305(2):288–97. https://doi.org/10.1006/abbi.1993.1425.
Oliw EH, Hörnsten L, Sprecher H. Oxygenation of 5,8,11-eicosatrienoic acid by prostaglandin H synthase-2 of ovine placental cotyledons: isolation of 13-hydroxy-5,8,11-eicosatrienoic and 11-hydroxy-5,8,12-eicosatrienoic acids. J Chromatogr B Biomed Sci Appl. 1997;690(1–2):332–7. https://doi.org/10.1016/s0378-4347(96)00372-6.
Hoffmann I, Hamberg M, Lindh R, Oliw EH. Novel insights into cyclooxygenases, linoleate diol synthases, and lipoxygenases from deuterium kinetic isotope effects and oxidation of substrate analogs. Biochim Biophys Acta. 2012;1821(12):1508–17. https://doi.org/10.1016/j.bbalip.2012.09.001.
Tsuboi K, Uyama T, Okamoto Y, Ueda N. Endocannabinoids and related N-acylethanolamines: biological activities and metabolism. Inflamm Regen. 2018;38:28. https://doi.org/10.1186/s41232-018-0086-5.
Priller J, Briley EM, Mansouri J, Devane WA, Mackie K, Felder CC. Mead ethanolamide, a novel eicosanoid, is an agonist for the central (CB1) and peripheral (CB2) cannabinoid receptors. Mol Pharmacol. 1995;48(2):288–92.
Retterstøl K, Woldseth B, Christophersen BO. Studies on the metabolism of [1-14 C]5.8.11-eicosatrienoic (Mead) acid in rat hepatocytes. Biochim Biophys Acta. 1995;1259(1):82–8. https://doi.org/10.1016/0005-2760(95)00150-b.
MaciasAli S, Yilmaz A, Kirma J, Moore SE, Woodside JV, Graham SF et al. Non-targeted LC-MS/MS metabolomic profiling of human plasma uncovers a novel Mediterranean diet biomarker panel. Research Square. https://doi.org/10.21203/rs.3.rs-3019157/v1.
Cleland LG, Gibson RA, Neumann MA, Hamazaki T, Akimoto K, James MJ. Dietary (n-9) eicosatrienoic acid from a cultured fungus inhibits leukotriene B4 synthesis in rats and the effect is modified by dietary linoleic acid. J Nutr. 1996;126(6):1534–40. https://doi.org/10.1093/jn/126.6.1534.
Cleland LG, James MJ, Proudman SM, Neumann MA, Gibson RA. Inhibition of human neutrophil leukotriene B4 synthesis in essential fatty acid deficiency: role of leukotriene A hydrolase. Lipids. 1994;29(3):151–5. https://doi.org/10.1007/bf02536722.
World Cancer Research Fund International. : Cancer risk factors. https://www.wcrf.org/diet-activity-and-cancer/risk-factors/. Accessed xx 2023.
Eynard AR, Jiang WG, Mansel RE. Eicosatrienoic acid (20:3 n-9) inhibits the expression of E-cadherin and desmoglein in human squamous cell carcinoma in vitro. Prostaglandins Leukot Essent Fatty Acids. 1998;59(6):371–7. https://doi.org/10.1016/s0952-3278(98)90098-9.
Hamazaki T, Nagasawa T, Hamazaki K, Itomura M. Inhibitory effect of 5,8,11-eicosatrienoic acid on angiogenesis. Prostaglandins Leukot Essent Fatty Acids. 2012;86(6):221–4. https://doi.org/10.1016/j.plefa.2012.04.004.
Inague A, Alecrim LC, Monteiro JS, Yoshinaga MY, Setubal JC, Miyamoto S, et al. Oxygen-induced pathological angiogenesis promotes intense lipid synthesis and remodeling in the retina. iScience. 2023;26(6):106777. https://doi.org/10.1016/j.isci.2023.106777.
Kinoshita K, Yoshioka M, Emoto Y, Yuri T, Yuki M, Koyama C, et al. Dietary effect of mead acid on DMBA–induced Breast cancer in female sprague–dawley rats. Int J Funct Nutr. 2020;1(2):7. https://doi.org/10.3892/ijfn.2020.7.
Pouchieu C, Chajès V, Laporte F, Kesse-Guyot E, Galan P, Hercberg S, et al. Prospective associations between plasma saturated, monounsaturated and polyunsaturated fatty acids and overall and Breast cancer risk - modulation by antioxidants: a nested case-control study. PLoS ONE. 2014;9(2):e90442. https://doi.org/10.1371/journal.pone.0090442.
Farag MA, Gad MZ. Omega-9 fatty acids: potential roles in inflammation and cancer management. J Genet Eng Biotechnol. 2022;20(1):48. https://doi.org/10.1186/s43141-022-00329-0.
Nguyen TT, Ziboh VA, Uematsu S, McCullough JL, Weinstein G. New model of a scaling dermatosis: induction of hyperproliferation in hairless mice with eicosa-5,8,11-trienoic acid. J Invest Dermatol. 1981;76(5):384–7. https://doi.org/10.1111/1523-1747.ep12520900.
Melton JL, Wertz PW, Swartzendruber DC, Downing DT. Effects of essential fatty acid deficiency on epidermal O-acylsphingolipids and transepidermal water loss in young pigs. Biochim Biophys Acta. 1987;921(2):191–7. https://doi.org/10.1016/0005-2760(87)90018-x.
Tiwari P, Nagatake T, Hirata SI, Sawane K, Saika A, Shibata Y, et al. Dietary coconut oil ameliorates skin contact hypersensitivity through mead acid production in mice. Allergy. 2019;74(8):1522–32. https://doi.org/10.1111/all.13762.
Saika A, Tiwari P, Nagatake T, Node E, Hosomi K, Honda T, et al. Mead acid inhibits retinol-induced irritant contact dermatitis via peroxisome proliferator-activated receptor alpha. Front Mol Biosci. 2023;10:1097955. https://doi.org/10.3389/fmolb.2023.1097955.
Polgreen PM, Comellas AP. Clinical phenotypes of cystic fibrosis carriers. Annu Rev Med. 2022;73:563–74. https://doi.org/10.1146/annurev-med-042120-020148.
Rivers JP, Hassam AG. Defective essential-fatty-acid metabolism in cystic fibrosis. Lancet. 1975;2(7936):642–3. https://doi.org/10.1016/s0140-6736(75)90121-x.
Gronowitz E, Mellström D, Strandvik B. Serum phospholipid fatty acid pattern is associated with bone mineral density in children, but not adults, with cystic fibrosis. Br J Nutr. 2006;95(6):1159–65. https://doi.org/10.1079/bjn20061778.
Van Biervliet S, Vanbillemont G, Van Biervliet JP, Declercq D, Robberecht E, Christophe A. Relation between fatty acid composition and clinical status or genotype in cystic fibrosis patients. Ann Nutr Metab. 2007;51(6):541–9. https://doi.org/10.1159/000114208.
Coste TC, Deumer G, Reychler G, Lebecque P, Wallemacq P, Leal T. Influence of pancreatic status and sex on polyunsaturated fatty acid profiles in cystic fibrosis. Clin Chem. 2008;54(2):388–95. https://doi.org/10.1373/clinchem.2007.094623.
Shrestha N, McCarron A, Rout-Pitt N, Donnelley M, Parsons DW, Hryciw DH. Essential fatty acid deficiency in cystic fibrosis Disease progression: role of genotype and sex. Nutrients. 2022;14(21):4666. https://doi.org/10.3390/nu14214666.
Watson H, Stackhouse C. Omega-3 fatty acid supplementation for cystic fibrosis. Cochrane Database Syst Rev. 2020;4(4):CD002201. https://doi.org/10.1002/14651858.cd002201.pub6.
Berdeaux O, Chardigny JM, Sébédio JL, Mairot T, Poullain D, Vatèle JM, et al. Effects of a trans isomer of arachidonic acid on rat platelet aggregation and eicosanoid production. J Lipid Res. 1996;37(10):2244–50. https://doi.org/10.1016/S0022-2275(20)37305-3.
Sicard B, Lagarde M. Incorporation of some eicosanoic acids into endothelial cells–effect on platelet inhibitory activity and prostacyclin production. Thromb Haemost. 1985; 22;53(2):264–7.
Lagarde M, Burtin M, Sprecher H, Dechavanne M, Renaud S. Potentiating effect of 5,8,11-eicosatrienoic acid on human platelet aggregation. Lipids. 1983;18(4):291–4. https://doi.org/10.1007/bf02534704.
Hamazaki T, Suzuki N, Widyowati R, Miyahara T, Kadota S, Ochiai H, et al. The depressive effects of 5,8,11-eicosatrienoic acid (20:3n-9) on osteoblasts. Lipids. 2009;44(2):97–102. https://doi.org/10.1007/s11745-008-3252-8.
Hamazaki K, Kawaguchi Y, Nakano M, Yasuda T, Seki S, Hori T, et al. Mead acid (20:3n-9) and n-3 polyunsaturated fatty acids are not associated with risk of posterior longitudinal ligament ossification: results of a case-control study. Prostaglandins Leukot Essent Fatty Acids. 2015;96:31–6. https://doi.org/10.1016/j.plefa.2015.01.003.
Yoshida H, Soh H, Sando K, Wasa M, Takagi Y, Okada A. Beneficial effects of n-9 eicosatrienoic acid on experimental bowel lesions. Surg Today. 2003;33(8):600–5. https://doi.org/10.1007/s00595-003-2572-9.
Miyake T, Furukawa S, Matsuura B, Yoshida O, Miyazaki M, Shiomi A, et al. Plasma fatty acid composition is associated with histological findings of nonalcoholic steatohepatitis. Biomedicines. 2022;10(10):2540. https://doi.org/10.3390/biomedicines10102540.
Acknowledgements
Not applicable.
Funding
Not applicable.
Author information
Authors and Affiliations
Contributions
H.K wrote original draft and reviewed and edited the manuscript. K.Y reviewed and edited the manuscript. Both authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Kawashima, H., Yoshizawa, K. The physiological and pathological properties of Mead acid, an endogenous multifunctional n-9 polyunsaturated fatty acid. Lipids Health Dis 22, 172 (2023). https://doi.org/10.1186/s12944-023-01937-6
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s12944-023-01937-6