Δ6 Desaturase Activity Research Articles

Associated factors of estimated desaturase activity in the EPIC-Potsdam study

Background and aimsAltered activity of desaturase enzymes may be involved in the development of metabolic diseases like type 2-diabetes. Desaturase activities might be modifiable by diet and lifestyle-related factors, but no study has systematically investigated such factors so far. We aimed to evaluate the association of demographic, anthropometric, dietary and lifestyle characteristics with estimated Δ5-, Δ6- and Δ9-desaturase activity. Methods and resultsA subsample (n = 1782) of the EPIC-Potsdam study was used for a cross-sectional analysis, involving men and women, mainly aged 35–65 years. Fatty acid (FA) product-to-precursor ratios, derived from the FA composition of erythrocyte membrane phospholipids, were used to estimate desaturase activities. Multiple linear regression models were used with estimated Δ5-, Δ6- and Δ9-desaturase activity as outcome and demographic (age, sex), anthropometric (BMI, WHR), dietary intake (FAs, carbohydrates) and lifestyle (physical activity, smoking, alcohol consumption) factors as exposure variables.Alcohol intake was positively associated with estimated Δ6- (explained variance in desaturase activity: 1.52%) and estimated Δ9-desaturase activity (explained variance: 5.53%). BMI and WHR showed a weak inverse association with estimated Δ5-desaturase activity (explained variance: BMI: 1.07%; WHR: 1.02%) and weak positive associations with estimated Δ6-(explained variance: BMI: 1.17%; WHR: 1.19%) and estimated Δ9-desaturase activities (explained variance: BMI: 0.70%; WHR: 0.96%). Age, sex, physical activity, smoking and dietary factors were only weakly associated with the estimated desaturase activities. ConclusionOur findings suggest that alcohol intake as well as obesity measures are associated with the FA ratios reflecting desaturase activity.

Trans-vaccenate is Δ13-desaturated by FADS3 in rodents

Fatty acid desaturases play critical roles in regulating the biosynthesis of unsaturated fatty acids in all biological kingdoms. As opposed to plants, mammals are so far characterized by the absence of desaturases introducing additional double bonds at the methyl-end site of fatty acids. However, the function of the mammalian fatty acid desaturase 3 (FADS3) gene remains unknown. This gene is located within the FADS cluster and presents a high nucleotide sequence homology with FADS1 (Δ5-desaturase) and FADS2 (Δ6-desaturase). Here, we show that rat FADS3 displays no common Δ5-, Δ6- or Δ9-desaturase activity but is able to catalyze the unexpected Δ13-desaturation of trans-vaccenate. Although there is no standard for complete conclusive identification, structural characterization strongly suggests that the Δ11,13-conjugated linoleic acid (CLA) produced by FADS3 from trans-vaccenate is the trans11,cis13-CLA isomer. In rat hepatocytes, knockdown of FADS3 expression specifically reduces trans-vaccenate Δ13-desaturation. Evidence is presented that FADS3 is the first "methyl-end" fatty acid desaturase functionally characterized in mammals.

Characterization of two Δ5 fatty acyl desaturases in abalone (Haliotis discus hannai Ino)

Long chain polyunsaturated fatty acid (LC-PUFA) biosynthesis is limited in many marine species, normally due to lack of Δ5 fatty acyl desaturase (Fad) activity. Among exceptions, abalone possesses considerable LC-PUFA conversion ability from C18 precursors. However, its characterization and relevant enzyme are not well characterized. Here we successfully cloned and characterized two Δ5 Fads in abalone (Haliotis discus hannai Ino). Two Δ5 Fad mRNA transcripts, Hdhfad1 (GQ 470626) and Hdhfad2 (GQ 466197), were found in abalone sharing 96.82% similarity for cDNA sequence and 96.58% similarity for their deduced amino acid sequences. Hdhfad1 cDNA is 1530bp in length with an opening reading frame (ORF) coding for 438 amino acids. Hdhfad2 cDNA is 1525bp in length with an ORF encoding for 439 amino acids. Both have characteristic features of front–end desaturase, including three histidine boxes, an N-terminal cytochrome b5 domain with heme-binding motif and transmembrane regions. Both Hdhfad1 and Hdhfad2 were expressed in tissues of abalone, especially in hepatopancreas and intestine. HdhFad1 possessed higher Δ5 desaturase activity but expressed at a lower level than HdhFad2. Both isoforms preferred 20:4n-3 than 20:3n-6 as substrate. These results should provide valuable information on the molecular evolution of Fads and better understanding of LC-PUFA biosynthesis in abalone.

Polyunsaturated fatty acid metabolism in enterocyte models: T84 cell line vs. Caco-2 cell line

Human colon carcinoma cell lines such as Caco-2 cells, model of mature enterocytes and T84 cells, model of crypt cells are useful to study interactions between nutrient processing and metabolic functions at intestinal level. Our study aimed at comparing the ability of Caco-2 and T84 cells (1) to incorporate dietary polyunsaturated fatty acids (PUFA), (2) to process them and (3) to sort them into neutral lipids (NL), free fatty acids (FFA) and phospholipids (PL). Caco-2 and T84 cells were exposed to a 7-day long supplementation with PUFA. The amounts of fatty acids accumulated and incorporated into the NL, FFA or PL fractions were higher in Caco-2 than in T84 cells. Caco-2 cells were able to significantly elongate C18 PUFA and C20 PUFA of both n-3 and n-6 families. In contrast, T84 cells were unable to elongate the n-6 fatty acids whereas elongation of n-3 fatty acids was detectable but marginal. Similarly, a Δ6 desaturase activity was observed in Caco-2 but not in T84 cells. In T84 cells, each exogenous fatty acid was predominantly accumulated in the PL fraction. In Caco-2 cells, C20 fatty acids and C18:2n-6 was preferentially accumulated in the PL fraction, while C22 PUFA and C18:3n-3 was preferentially accumulated in the NL fraction. Overall, this study has shown that Caco-2 and T84 cells, as models of intestinal mucosal cells, present large differences in PUFA accumulation capacity, specific elongase and desaturase activities and distribution pattern of exogenous PUFA and of their metabolites in the lipid classes.

Exploring the Biosynthesis of Unsaturated Fatty Acids in Bacillus cereus ATCC 14579 and Functional Characterization of Novel Acyl-Lipid Desaturases

At low temperatures, Bacillus cereus synthesizes large amounts of unsaturated fatty acids (UFAs) with double bonds in positions Δ5 and Δ10, as well as Δ5,10 diunsaturated fatty acids. Through sequence homology searches, we identified two open reading frames (ORFs) encoding a putative Δ5 desaturase and a fatty acid acyl-lipid desaturase in the B. cereus ATCC 14579 genome, and these were named BC2983 and BC0400, respectively. Functional characterization of ORFs BC2983 and BC0400 by means of heterologous expression in Bacillus subtilis confirmed that they both encode acyl-lipid desaturases that use phospholipids as the substrates and have Δ5 and Δ10 desaturase activities. Thus, these ORFs were correspondingly named desA (Δ5 desaturase) and desB (Δ10 desaturase). We established that DesA utilizes ferredoxin and flavodoxins (Flds) as electron donors for the desaturation reaction, while DesB preferably employs Flds. In addition, increased amounts of UFAs were found when B. subtilis expressing B. cereus desaturases was subjected to a cold shock treatment, indicating that the activity or the expression of these enzymes is upregulated in response to a decrease in growth temperature. This represents the first work reporting the functional characterization of fatty acid desaturases from B. cereus.

The role of desaturases in the biosynthesis of marking pheromones in bumblebee males

Bumblebee males (Hymenoptera) produce species-specific labial gland secretions called marking pheromones (MPs). MPs generally consist of terpenoids and fatty-acid-derived aliphatic compounds with various chain lengths predominantly containing one or no double bonds. The unsaturated fatty-acid-derived MP components were hypothesized to be produced by fatty acid desaturases (FADs) that exhibit diverse substrate specificities. To address this hypothesis, we isolated and functionally characterized FADs from three bumblebee species: Bombus lucorum, Bombus terrestris, and Bombus lapidarius. By employing RNA sequencing of the male labial glands and fat bodies of B. lucorum and B. terrestris, we identified five paralogous FAD-like sequences but only two FAD lineages were abundant and differentially expressed in the labial glands. We found that abundant FAD lineages were also expressed in the labial gland and fat body of Bombus lapidarius. Functional characterization of FADs in a yeast expression system confirmed that Δ4-FADs exhibited a unique Δ4-desaturase activity exclusively on 14-carbon fatty acyls and Δ9-FADs displayed Δ9-desaturase activity on 14- to 18-carbon fatty acyls. These results indicate that Δ9-FADs are involved in the biosynthesis of major unsaturated components of MPs in B. lucorum and B. lapidarius despite the diverse MP composition of these bumblebee species. The contribution of lipases, acyltransferases, esterases, and fatty acid reductases to production of the species-specific MP composition is also discussed in light of the transcriptomic data obtained in this study.

Fatty acid desaturase 2 (FADS2) insertion/deletion polymorphism impact on muscle fatty acid profile in European grayling (Thymallus thymallus)

An insertion (In)/deletion (Del) polymorphism in the fatty acid desaturase 2 (FADS2) gene, which codes for Δ6-desaturase, was for the first time observed in fish. The polymorphism is located in the seventh intron of FADS2 and the insertion consists of eleven repeats of CTGT (44 bp) with an allelic frequency, for the insertion, of 39 %. The polymorphism was associated with a modulation in Δ6-desaturase activity as significant effects on the ratio of EPA or DHA to their precursors were found (P< 0·001). A different distribution of SFA, MUFA and PUFA among the In/In, In/Del and Del/Del groups was also detected in fish fillet. The results suggest that genetic selection for this marker might improve the ability of European grayling to utilise dietary n-3 long-chain PUFA precursors, as Δ6-desaturase is the rate-limiting enzyme in the production of EPA and DHA from α-linolenic acid.

Comparative effects of well-balanced diets enriched in α-linolenic or linoleic acids on LC-PUFA metabolism in rat tissues

The intake of the essential fatty acid precursor α-linolenic acid (ALA) contributes to ensure adequate n-3 long-chain polyunsaturated fatty acid (LC-PUFA) bioavailability. Conversely, linoleic acid (LA) intake may compromise tissue n-3 PUFA status as its conversion to n-6 LC-PUFA shares a common enzymatic pathway with the n-3 family. This study aimed to measure dietary ALA and LA contribution to LC-PUFA biosynthesis and tissue composition. Rats were fed with control or experimental diets moderately enriched in ALA or LA for 8 weeks. Liver Δ6- and Δ5-desaturases were analyzed and FA composition was determined in tissues (red blood cells, liver, brain and heart). Hepatic Δ6-desaturase activity was activated with both diets, and Δ5-desaturase activity only with the ALA diet. The ALA diet led to higher n-3 LC-PUFA composition, including DHA in brain and heart. The LA diet reduced n-3 content in blood, liver and heart, without impacting n-6 LC-PUFA composition. At levels relevant with human nutrition, increasing dietary ALA and reducing LA intake were both beneficial in increasing n-3 LC-PUFA bioavailability in tissues.

Iron supplementation decreases plasma zinc but has no effect on plasma fatty acids in non-anemic women

Limited information is available on the role of iron in fatty acid metabolism in humans. We hypothesized that iron supplementation will increase desaturase activity, and so, the aim of this study was to determine the effect of iron supplementation on fatty acid desaturase activity in young women. Participants were randomly assigned to a control group (CG) or supplementation group (SG) who were provided with 37.4 mg of elemental iron daily for 12 weeks. Forty women completed the trial, n = 19 in CG and n = 21 in SG. The mean ages were 25.2 and 24.6 years, and body mass indices were 21.8 and 21.2 (kg/m2) in CG and SG, respectively. Serum ferritin concentrations increased significantly (P < .01) in subjects assigned to SG but were unchanged in CG. Serum iron concentrations were not significantly changed. Plasma zinc concentrations at the end of the intervention were similar to baseline values for individuals in CG but were decreased significantly (P = .004) in SG. Plasma fatty acids, phospholipid fatty acids, and desaturase activities, expressed as precursor-to-product ratios, were not significantly affected by the intervention, although in SG the concentration of serum ferritin was correlated positively (P < .05) with Δ6-desaturase activity. Supplementing non-anemic women with low dose iron improves iron status but has no significant effect on desaturase activity. The lack of a clear effect on an indirect indicator of desaturase activity may be related to the antagonism between iron and zinc, as illustrated by the decrease in plasma zinc concentrations in women who were supplemented with iron.

Fibrate treatment induced quantitative and qualitative HDL changes associated with an increase of SR-BI cholesterol efflux capacities in rabbits

Fibrates are widely used as lipid lowering drugs acting as peroxisome proliferator-activated receptors α (PPARα) agonists and modulating the expression of several genes involved in lipid and lipoprotein metabolism. Much less is known on the effect of fibrates in HDL structure and composition. Therefore, we examined whether fenofibrate induces quantitative and/or qualitative modifications in HDL metabolism in the rabbit, an animal that, contrary to rodents and similar to humans, is less sensitive to peroxisome proliferators. We first demonstrated that 3-week treatment with fenofibrate (250 mg/kg/day) induced an important increase in serum apolipoprotein A-I, HDL-cholesterol and HDL-phospholipids concentrations and a relative enrichment in HDL cholesteryl ester content. Moreover, the fatty acid profiles from fenofibrate-treated rabbits displayed a dramatic increase in the serum or HDL C18:3 ω6 to C18:2 ω6 ratio suggesting higher Δ6 desaturase activity. In addition, HDL from fenofibrate-treated animals exhibited higher relative proportions of sphingomyelin, phosphatidylinositol and phosphatidylethanolamine. We then reported that fenofibrate induced major changes in the physical characteristics of HDL, mainly a higher size and a faster mobility on agarose gel electrophoresis. Finally, serum or HDL from treated rabbits exhibited higher capacity to promote cholesterol efflux from Scavenger receptor class B type I (SR-BI)-rich Fu5AH cells compared to controls. Our findings demonstrate that fenofibrate has beneficial effects in rabbits by increasing the mass of the circulating HDL pool and by modifying their composition transforming them as better acceptors of cellular cholesterol through SR-BI pathway. These effects of fenofibrate might contribute to its benefits on the prevention and treatment of atherosclerosis.

Association of polymorphisms in FADS gene with age-related changes in serum phospholipid polyunsaturated fatty acids and oxidative stress markers in middle-aged nonobese men

Background:To investigate the association of FADS gene polymorphisms with age-related changes in polyunsaturated fatty acids (PUFAs) in serum phospholipids and oxidative stress markers.Methods:We genotyped 122 nonobese men aged 35–59 years without any known diseases at baseline for rs174537 near FADS1 (FEN1 rs174537G > T), FADS2 (rs174575, rs2727270), and FADS3 (rs1000778), and followed them for 3 years.Results:Among the four single-nucleotide polymorphisms, the minor variants of rs174537 and rs2727270 were significantly associated with lower concentrations of long-chain PUFAs. However, rs174537G > T showed stronger association. At baseline, men with the rs174537T allele had lower arachidonic acid (AA) and AA/linoleic acid (LA), and higher interleukin (IL)-6 levels than rs174537GG counterparts. After 3 years, rs174537GG men had significantly increased AA (P = 0.022), AA/dihomo-γ-linolenic acid (DGLA) (P = 0.007), docosapentaenoic acid (DPA), low-density lipoprotein (LDL) cholesterol, and oxidized LDL (ox-LDL), but decreased eicosatrienoic acid. The rs174537T group showed significantly increased γ-linolenic acid and ox-LDL, and decreased eicosadienoic acid, eicosapentaenoic acid (EPA)/α-linolenic acid (ALA), and IL-6. After 3 years, the rs174537T group had lower AA (P < 0.001), AA/DGLA (P = 0.019), EPA, DPA, EPA/ALA, and urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) (P = 0.011) than rs174537GG. Changes in AA (P = 0.001), AA/DGLA (P = 0.017), EPA, DPA, EPA/ALA, and urinary 8-epi-PGF2α (P < 0.001) were significantly different between the groups after adjusting for baseline values. Overall, changes in AA positively correlated with changes in urinary 8-epi-PGF2α (r = 0.249, P = 0.007), plasma ox-LDL (r = 0.199, P = 0.045), and serum IL-6 (r = 0.289, P = 0.004).Conclusion:Our data show that FADS polymorphisms can affect age-associated changes in serum phospholipid long-chain PUFAs, Δ5-desaturase activity, and oxidative stress in middle-aged nonobese men. In particular, the rs174537T allele did not show the age-associated increases in AA and Δ5-desaturase activity seen with the rs174537GG genotype.

Role of LOXs and COX-2 on FAK activation and cell migration induced by linoleic acid in MDA-MB-231 breast cancer cells

Epidemiological studies and animal models suggest a link between high levels of dietary fat intake and an increased risk of developing breast cancer. Particularly, free fatty acids (FFAs) are involved in several processes, including proliferation, migration and invasion, in breast cancer cells. Linoleic acid (LA) is a dietary n-6 polyunsaturated fatty acid that is known to induce proliferation and invasion in breast cancer cells. So far, however, the contribution of LA to focal adhesion kinase (FAK) activation and cell migration in breast cancer cells has not been studied. Here, we show that LA promotes FAK and Src activation, as well as cell migration, in MDA-MB-231 breast cancer cells. FAK activation and cell migration require Src, Gi/Go, COX-2 and LOXs activities, whereas both are independent of Δ6 desaturase activity. In addition, we show that cell migration requires FAK activity, whereas FAK activation requires Src activity, thus suggesting a reciprocal catalytic activation mechanism of FAK and Src. In summary, our findings show that LA induces FAK activation and cell migration in MDA-MB-231 breast cancer cells.

Fatty acid profile of the milk of cows reared in the mountain region of Poland

An appropriate composition of milk fatty acids (FA) improves the nutritional value of milk and milk products, and improves milk processing. Polish dairy farms in the mountainous region are rather small, animal nutrition there is based on locally produced forages and this, together with the transitional climate zone brings about seasonal changes in FA composition of milk. The aim of the study was to evaluate the composition of FA in bovine milk fat in relation to fat intake in forages and their FA profiles. The study involved 5 herds reared in low-input mountain farms located at an altitude of 670-780 m above sea level (Beskid Mountains). The cows were fed forages produced locally. FAs in forages and milk samples were subjected to gas chromatography. Highest fat intake observed in grazing season (4·2-4·7%) and high amounts of polyunsaturated FA in forages from that period (51·8-64·1 g/100 g FA) resulted in a markedly high content of valuable FAs: t-11 C18:1 (3·22 g/100 g FA), c-9, t-11 C18:2 (CLA; 1·20 g/100 g FA) in milk. Lower fat intake of forages containing high amount of SFA (32·42-38·83 g/100 g FA) in the indoor period resulted in changes in milk composition. The content of total short-chain saturated FA (SCFA) was highest in winter and early spring samples (14·10 and 13·44 g/100 g FA, respectively), like the amounts of myristic C14:0 and palmitic C16:0 acids (11·80 and 37·92 g/100 g FA). Total odd- and branched-chain fatty acids (OBCFA; 6·58 g/100 g FA) content was highest at the beginning of the grazing period. Fresh grass consumed by cows promoted the activity of Δ(9)-desaturase in mammary gland as evidenced by higher C14:1 : C14:0 (0·054) and C16:1 : C16:0 (0·026) ratios in grazing than in the indoor periods.

Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells

BackgroundDiabetic retinopathy is a major complication of dysregulated hyperglycemia. Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 ω-3) and eicosapentaenoic acid (EPA, 20:5 ω-3). The influence of dietary omega-3 PUFA on brain zinc metabolism has been previously implied. Zn2+ is essential for the activity of Δ6 desaturase as a co-factor that, in turn, converts essential fatty acids to their respective long chain metabolites. Whether essential fatty acids (EFAs) α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood.MethodsRF/6A cells were treated with different concentrations of high glucose, α-linolenic acid and linoleic acid and Zn2+. The alterations in mitochondrial succinate dehydrogenase enzyme activity, cell membrane fluidity, reactive oxygen species generation, SOD enzyme and vascular endothelial growth factor (VEGF) secretion were evaluated.ResultsStudies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by both linoleic acid (LA) and α-linolenic acid (ALA), while the saturated fatty acid, palmitic acid was ineffective. A dose–response study with ALA showed that the activity of the mitochondrial succinate dehydrogenase enzyme was suppressed at all concentrations of glucose tested to a significant degree. High glucose enhanced fluorescence polarization and microviscocity reverted to normal by treatment with Zn2+ and ALA. ALA was more potent that Zn2+. Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity. ALA suppressed ROS generation to a significant degree in a dose dependent fashion and raised SOD activity significantly. ALA suppressed high-glucose-induced VEGF secretion by RF/6A cells.ConclusionsThese results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.

Isolation of a Δ5 Desaturase Gene from Euglena gracilis and Functional Dissection of Its HPGG and HDASH Motifs

Delta (Δ) 5 desaturase is a key enzyme for the biosynthesis of health-beneficial long chain polyunsaturated fatty acids such as arachidonic acid (ARA, C20:4n-6), eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) via the “desaturation and elongation” pathways. A full length Δ5 desaturase gene from Euglena gracilis (EgΔ5D) was isolated by cloning the products of polymerase chain reaction with degenerate oligonucleotides as primers, followed by 5′ and 3′ rapid amplification of cDNA ends. The whole coding region of EgΔ5D was 1,350 nucleotides in length and encoded a polypeptide of 449 amino acids. BlastP search showed that EgΔ5D has about 39 % identity with a Δ5 desaturase of Phaeodactylum tricornutum. In a genetically modified dihomo-gamma-linoleic acid (DGLA, C20:3n-6) producing Yarrowia lipolytica strain, EgΔ5D had strong Δ5 desaturase activity with DGLA to ARA conversion of more than 24 %. Functional dissection of its HPGG and HDASH motifs demonstrated that both motifs were important, but not necessary in the exact form as encoded for the enzyme activity of EgΔ5D. A double mutant EgΔ5D-34G158G with altered sequences within both HPGG and HDASH motifs was generated and exhibited Δ5 desaturase activity similar to the wild type EgΔ5D. Codon optimization of the N-terminal region of EgΔ5D-34G158G and substitution of the arginine with serine at residue 347 improved substrate conversion to 27.6 %.Electronic supplementary materialThe online version of this article (doi:10.1007/s11745-012-3690-1) contains supplementary material, which is available to authorized users.

Polymorphisms in FADS2 correlated with altered desaturase activity in a type‐2 diabetic cohort

Recent evidence reveals that single nucleotide polymorphisms (SNP) in fatty acid desaturase 2 (FADS2) is correlated with alteration in blood fatty acid profile in some ethnic groups. We aimed to examine effects of FADS2 (intronic SNP, rs174589) on Δ6 and Δ5 desaturase activities based on ratios of 18:3n‐6/18:2n‐6 and 20:4n‐6/20:3n‐6 respectively. In 2008, we cross‐sectionally analyzed erythrocyte fatty acids in type 2 diabetic patients (n=702) recruited from the Diabetes Management through Integrated Delivery System (DMIDS) cohort established in Taiwan. Frequencies of rs174589 genotypes GG, GC and CC were 0.739, 0.234 and 0.027 respectively. Levels of hemoglobin A1c in CC genotypes were significantly different from those of GC and GG genotypes. Δ6 desaturase activity (18:3n‐6/18:2n‐6) was significantly reduced in GC (0.005±0.003, p=0.003) and CC (0.004±0.003, p=0.025) than GG genotypes (0.006±0.003). Similarly, Δ5 desaturase activity (20:4n‐6/20:3n‐6) was significantly diminished in C allele carriers than the GG homozygotes (p&lt;0.05). In conclusion, rs174589 in FADS2 is associated with Δ6 and Δ5 desaturase activities in type 2 diabetes patients and impact of these alterations in fatty acids profiles on clinical parameters warrants further investigation.

Barramundi (Lates calcarifer) desaturase with Δ6/Δ8 dual activities

Barramundi is a commercially farmed fish in Australia. To examine the potential for barramundi to metabolise dietary α-linolenic acid (ALA, 18:3 n-3), the existence of barramundi desaturase enzymes was examined. A putative fatty acid Δ6 desaturase was cloned from barramundi liver and expressed in yeast. Functional expression revealed Δ6 desaturase activity with both the 18 carbon (C(18)) and C(24) n-3 fatty acids, ALA and 24:5 n-3 as well as the C(18) n-6 fatty, linoleic acid (LA, 18:2 n-6). Metabolism of ALA was favoured over LA. The enzyme also had Δ8 desaturase activity which raises the potential for synthesis in barramundi of omega-3 (n-3) long chain polyunsaturated fatty acids from ALA via a pathway that bypasses the initial Δ6 desaturase step. Our findings not only provide molecular evidence for the fatty acid desaturation pathway in the barramundi but also highlight the importance of taking extracellular fatty acid levels into account when assessing enzyme activity expressed in Saccharomyces cerevisiae.

Low linoleic acid may facilitate Δ6 desaturase activity and docosahexaenoic acid accretion in human fetal development

The n-3 and n-6 fatty acids are transferred across the placenta with consistently higher 22:6n-3 and lower 18:2n-6 in fetal than maternal plasma. This study sought to determine whether maternal and fetal cord blood red blood cell (RBC) phospholipid fatty acids show similar saturation with 22:6n-3, and also addressed the relationship between 18:2n-6 and Δ6 desaturase product/precursor ratios for 97 mothers and newborns. Despite higher fetal than maternal plasma phospholipid 22:6n-3, the maternal and fetal RBC phospholipid 22:6n-3 showed similar curvilinear relationships to the plasma phospholipid 22:6n-3. Risk of failure to achieve high RBC phospholipid 22:6n-3 increased sharply below a plasma phospholipid 22:6n-3 of 6.5g/100g fatty acids. Higher maternal and fetal 18:2n-6 was associated with lower RBC phospholipid 22:6n-3/22:5n-3, 22:5n-6/22:4n-6 and 18:3n-6/18:2n-6. These findings suggest low placental transfer of 18:2n-6 may be a specific mechanism to prevent inhibition of fetal Δ6 desaturase and facilitate fetal cellular phospholipid 22:6n-3 accretion.

Recent insights into the relation of Δ5 desaturase and Δ6 desaturase activity to the development of type 2 diabetes

The Δ5 desaturase (D5D) and Δ6 desaturase (D6D) are key enzymes in the metabolism of polyunsaturated fatty acids. This review aims to summarize recent advances towards understanding the relation of the activities of D5D and D6D to the development of type 2 diabetes. Prospective studies that investigated fatty acid product-to-precursor ratios in blood as estimates of desaturase activity reported a clear inverse relation of D5D activity and a strong direct relation of D6D activity to diabetes incidence. Due to the prospective design and comprehensive confounder adjustment in these studies, confounding and reverse causation are unlikely explanations for these findings. Furthermore, studies on genetic variation in the FADS1 and FADS2 genes, which encode D5D and D6D, also point to an influence of D5D and D6D activity on glucose metabolism. The inverse relation of D5D activity and the direct relation of D6D activity to diabetes risk have been corroborated by a Mendelian randomization approach recently. These recent studies suggest an important role of D5D and D6D activities for the development of type 2 diabetes. Factors which influence the activities of these desaturases are likely to be of public health relevance.

Maintenance of Arachidonic Acid and Evidence of Δ5 Desaturation in Cats Fed γ‐Linolenic and Linoleic Acid Enriched Diets

Cats have limited Δ6 desaturase activity. However, γ-linolenate (GLA) feeding may by-pass the Δ6 desaturase step allowing arachidonate (ARA) accumulation via Δ5-desaturation. Alternatively, high dietary linoleate (LNA) may induce limited Δ6 desaturase also resulting in ARA accumulation. Fatty acid profiles were determined after feeding high LNA, high GLA, or adequate LNA diets. Adult female cats (n=29) were assigned to one of three groups and fed for 8weeks. Plasma samples were collected at weeks 0, 2, 4 and 8 for plasma triacylglycerol (TAG), total cholesterol (TC), lipoprotein (LP), and plasma and red blood cell membrane phospholipid fatty acid determinations. Time, but no diet, effects were observed for TAG, TC, and LP fractions at weeks 2 and 4 with significant increases likely due to increased dietary fat. However, all values were within feline normal limits. The GLA diet resulted in increased dihomo-γ-linolenic acid (DGLA) and ARA as early as week 2, supporting a ∆5 desaturase. Further evidence of Δ5 desaturase was found at high dietary LNA with the appearance of a novel fatty acid, 20:3 ∆7, 11, 14, apparently formed via ∆5 desaturation and chain elongation of LNA. However, Δ6 desaturase induction at high dietary LNA concentration was not observed. Cats are able to maintain plasma and red blood cell ARA when fed a practical diet containing GLA using what appears to be an active Δ5 desaturase enzyme.