Conversion Of Α-linolenic Acid Research Articles

Evaluation of Influencing Factors on Metabolism of Land-Based n-3 Poly Unsaturated Fatty Acids-The KoALA Study.

This study aimed to investigate the impact of influencing factors (sex, eicosapentaenoic acid (EPA) status at baseline, linoleic acid (LA) intake, milk fat intake) on the conversion of α-linolenic acid (ALA) obtained from linseed oil into its long-chain metabolites. In addition, the effect of ALA on cardiovascular risk markers was investigated. This study used a parallel design approach by randomly assigning the 134 subjects to one of four diets (high in LA (HLA); low in LA (LLA); high in milk fat (MF); control (Western diet)) each enriched with linseed oil (10 en%, 22-27 mL ≙ 13-16 g ALA). Blood samples were taken at baseline and after 4, 8, and 12 weeks of dietary intervention. The study was fully completed by 105 subjects (57.4 ± 12.1 years; 65.7% female). Results showed that ALA (296-465%), C-20:4n3 (54-140%), and EPA (37-73%) concentrations in erythrocytes increased in all groups (p < 0.01). In contrast, docosahexaenoic acid (19-35%, p < 0.01) and n-3 index (10-21%, p < 0.05) dropped in the HLA, LLA, and control groups. An increase in C-22:5n3 was only observed in the MF (36%) and control groups (11%) (p < 0.05). In addition, an increase in LA (7-27%) was found in the HLA, LLA, and control groups, whereas C-20:3n6 (16-22%), arachidonic acid (10-16%), C-22:4n6 (12-30%), and C-22:5n6 (32-47%) decreased (p < 0.01). The conversion into EPA was higher in men than in women (69 vs. 39%, p = 0.043) and in subjects with low EPA status compared to participants with high EPA status (79 vs. 29%, p < 0.001). A high LA status attenuates the conversion rate. In line with the literature, no clear effects on blood lipids and parameters of glucose metabolism were found in relation to ALA supplementation.

Enriched Fresh Pasta with a Sea Bass By-Product, a Novel Food: Fatty Acid Stability and Sensory Properties throughout Shelf Life.

A by-product from the filleting of sea bass (Dicentrachus labrax) was used to manufacture enriched pasta. The research aimed at achieving an increase of protein and unsaturated fatty acid contents, making innovative and healthy pasta products that are able to step up fish consumption. Two different kind of cereals were used to make fresh pasta, which were subjected to frozen storage with the addition or not of a rosemary antioxidant. The developed pastas were analyzed by physicochemical methods. Proximal analysis demonstrated an improvement of nutritional values on those of a common pasta. Fatty acid profiles, acidity indices, and TBARS (Thiobarbituric acid reactive substances) index confirmed the stability of fat and effective protection against oxidation, especially in pasta with added antioxidant. The cooking time for pasta was set at 90 s, and color parameters were modified due to the incorporation of fish in the pasta-making process. An enrichment in fatty acids ω-3 and ω-6 was also confirmed. The conversion of α-linolenic acid (ALA) in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in frozen storage was detected, which remained stable during 90 days. Finally, sensory profiles of enriched pasta were found to be adequate and improved following the addition of an antioxidant due to a decrease of negative attributes associated with oxidation.

Effects of the flavonol quercetin and α-linolenic acid on n-3 PUFA status in metabolically healthy men and women: a randomised, double-blinded, placebo-controlled, crossover trial.

Increased dietary intake and tissue status of the long-chain n-3 PUFA, EPA and DHA, is associated with cardiovascular benefits. Epidemiological and animal studies suggest that concomitant nutritive intake of flavonoids may increase the conversion of α-linolenic acid (ALA) to longer-chain n-3 fatty acids EPA and DHA. We investigated the effects of increased ALA intake on fatty acid composition of serum phospholipids and erythrocytes in metabolically healthy men and women and whether fatty acid profiles and ALA conversion were affected by regular quercetin intake or sex. Subjects (n 74) were randomised to receive at least 3·3 g/d ALA with either 190 mg/d quercetin (ALA+quercetin) or placebo (ALA+placebo) in a double-blinded, placebo-controlled, crossover trial with 8-week intervention periods separated by an 8-week washout period. A total of seven subjects dropped out for personal reasons. Data from the remaining sixty-seven subjects (thirty-four males and thirty-three females) were included in the analysis. Both interventions significantly increased serum phospholipid ALA (ALA+placebo: +69·3 %; ALA+quercetin: +55·8 %) and EPA (ALA+placebo: +37·3 %; ALA+quercetin: +25·5 %). ALA + quercetin slightly decreased DHA concentration by 9·3 %. Erythrocyte ALA and EPA significantly increased with both interventions, whereas DHA decreased. Fatty acid composition did not differ between sexes. We found no effect of quercetin. Intake of 3·6 g/d ALA over an 8-week period resulted in increased ALA and EPA, but not DHA, in serum phospholipids and erythrocytes. Neither quercetin supplementation nor sex affected the increment of ALA and relative proportions of n-3 PUFA in serum phospholipids and erythrocytes.

Estrogen increases the conversion of α‐linolenic acid to docosahexaenoic acid in ovariectomized mice

n‐3 polyunsaturated fatty acids (PUFA), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial health effects. The conversion of α‐linolenic acid (ALA) to EPA and DHA is low, especially in males compared to females and varies in the literature. Estrogen (E2) is suggested to affect ALA conversion but few studies have confirmed the E2 effect. Our objective was to determine the independent effect of E2 on n‐3 PUFA levels in serum and various tissues in female ovariectomized mice fed diets with low and high ALA. After 7 weeks exposure to an E2 pellet, mice were randomized to a corn oil‐based basal diet or an ALA‐rich flaxseed diet (FS) with or without removal of the E2 pellet for 4 weeks. E2 responsiveness was indicated by the 269% higher (P&lt;0.001) uterus weight in E2‐ treated mice compared to those with E2 pellet removed. FS‐fed mice had higher proportions of ALA, EPA and DHA in total lipids extracted from serum, liver and brain. E2‐treated mice had higher serum (15.1%; P&lt;0.001) and liver (18.2%; P&lt;0.001) DHA but not brain DHA. EPA levels were not affected by E2. There was a diet × E2 interaction for ALA in the liver where the FS+E2 group had lower ALA compared to FS‐E2. In conclusion, E2 results in higher serum and liver DHA, does not affect brain DHA and does not affect EPA in any of the tissues measured. This finding may help explain the variability in ALA effect in studies involving males and females.Grant Funding Source: NSERC

Deposition of docosahexaenoic acid (DHA) is limited in forebrain of young obese fa/ fa Zucker rats fed a diet high in α-linolenic acid but devoid of DHA

Docosahexaenoic acid (DHA) is required for neurotransmitter synthesis and learning. Conversion of α-linolenic acid (ALA) to DHA is considered adequate to support brain function in youth, but it is unknown if brain DHA can be maintained in insulin resistant states. This study investigated brain fatty acid and desaturase activities in young insulin resistant Zucker rats on diets with and without DHA. Male fa/fa and lean rats were fed diets enriched with flaxseed (FXO, ALA: 35.5% fatty acids), menhaden (MO, DHA: 9.2%) or safflower oil (SO, linoleic acid: 54.1%) for 9 weeks, n=8 per diet per genotype. Compared to lean, the 15 week old fa/fa rats were obese (56% heavier) and insulin-resistant (>18-fold in homeostasis model assessment of insulin resistance). The forebrain of fa/fa rats had higher palmitoleic (16:1n-7) and dihomo-γ-linolenic (20:3n-6) acids, and higher Δ9, Δ6 but lower Δ5 (all P≤.006) desaturase indices than lean. The Δ9 and Δ6 desaturase indices positively, while the Δ5 negatively (all P≤.01) correlated with insulin resistance. The Δ9 desaturase index positively correlated with adiposity index. The percentage of forebrain DHA of fa/fa rats was lower ( P=.011) than lean rats when fed FXO diet while there was no difference ( P>.05) between fa/fa and lean rats fed MO or SO diet. Thus, the alterations in the fatty acid and desaturase indices in the brain were consistent inhibited forebrain synthesis of DHA in the fa/fa rats. ALA may not have potential to effectively serve as a precursor for synthesizing DHA for youth forebrain during insulin resistance since Δ5 desaturase activity is limited.

OVER-EXPRESSION OF GENE ENCODING FATTY ACID METABOLIC ENZYMES IN FISH

Eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) have important nutritional benefits in humans. EPA and DHA are mainly derived from fish, but the decline in the stocks of major marine capture fishes could result in these fatty acids being consumed less. Farmed fish could serve as promising sources of EPA and DHA, but they need these fatty acids in their diets. Generation of fish strains that are capable of synthesizing enough amounts of EPA/DHA from the conversion of α-linolenic acid (LNA, 18:3n-3) rich oils can supply a new EPA/DHA source. This may be achieved by over-expression of genes encoding enzymes involved in HUFA biosynthesis. In aquaculture, the successful of this technique would open the possibility to reduce the enrichment of live food with fish oils for marine fish larvae, and to completely substitute fish oils with plant oils without reducing the quality of flesh in terms of EPA and DHA contents. Here, three genes, i.e. Δ6-desaturase-like (OmΔ6FAD), Δ5-desaturase-like (OmΔ5FAD) and elongase-like (MELO) encoding EPA/DHA metabolic enzymes derived from masu salmon (Oncorhynchus masou) were individually transferred into zebrafish (Danio rerio) as a model to increase its ability for synthesizing EPA and DHA. Fatty acid analysis showed that EPA content in whole body of the second transgenic fish generation over-expressing OmΔ6FAD gene was 1.4 fold and that of DHA was 2.1 fold higher (P&lt;0.05) than those in non-transgenic fish. The EPA content in whole body of transgenic fish over-expressing OmΔ5FAD gene was 1.21-fold, and that of DHA was 1.24-fold higher (P&lt;0.05) than those in nontransgenic fish. The same patterns were obtained in transgenic fish over-expressing MELO gene. EPA content was increased by 1.30-fold and DHA content by 1.33-fold higher (P&lt;0.05) than those in non-transgenic fish. The results of studies demonstrated that fatty acid content of fish can be enhanced by over-expressing gene encoding enzymes involved in fatty acid biosynthesis, and perhaps this could be applied to tailor farmed fish as even better sources of valuable human food.

Competition between 24:5n-3 and ALA for Δ6 desaturase may limit the accumulation of DHA in HepG2 cell membranes

The use of Delta 6 desaturase (D6D) twice in the conversion of alpha-linolenic acid (ALA; 18:3n-3) to docosahexaenoic acid (DHA; 22:6n-3) suggests that this enzyme may play a key regulatory role in the synthesis and accumulation of DHA from ALA. We examined this using an in vitro model of fatty acid metabolism to measure the accumulation of the long-chain metabolites of ALA in HepG2 cell phospholipids. The accumulation of ALA, eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3), and 24:5n-3 in cell phospholipids was linearly related to the concentration of supplemented ALA over the range tested (1.8-72 microM). The accumulation of the post-D6D products of 22:5n-3, 24:6n-3 and DHA, in cell phospholipids was saturated at concentrations of >18 microM ALA. Supplementation of HepG2 cells with preformed DHA revealed that, although the accumulation of DHA in cell phospholipids approached saturation, the level of DHA in cell phospholipids was significantly greater compared with the accumulation of DHA from ALA, indicating that the accumulation of DHA from ALA was not limited by incorporation. The parallel pattern of accumulation of 24:6n-3 and DHA in response to increasing concentrations of ALA suggests that the competition between 24:5n-3 and ALA for D6D may contribute to the limited accumulation of DHA in cell membranes.

Conversion of α-linolenic acid in humans is influenced by the absolute amounts of α-linolenic acid and linoleic acid in the diet and not by their ratio

Human in vivo data on dietary determinants of alpha-linolenic acid (ALA; 18:3n-3) metabolism are scarce. We examined whether intakes of ALA or linoleic acid (LA; 18:2n-6) or their ratio influences ALA metabolism. During 4 wk, 29 subjects received a control diet (7% of energy from LA, 0.4% of energy from ALA, ALA-to-LA ratio = 1:19). For the next 6 wk, a control diet, a low-LA diet (3% of energy from LA, 0.4% of energy from ALA, ratio = 1:7), or a high-ALA diet (7% of energy from LA, 1.1% of energy from ALA, ratio = 1:7) was consumed. Ten days before the end of each dietary period, [U-13C]ALA was administered orally for 9 d. ALA oxidation was determined from breath. Conversion was estimated by using compartmental modeling of [13C]- and [12C]n-3 fatty acid concentrations in fasting plasma phospholipids. Compared with the control group, ALA incorporation into phospholipids increased by 3.6% in the low-LA group (P = 0.012) and decreased by 8.0% in the high-ALA group (P < 0.001). In absolute amounts, it increased by 34.3 mg (P = 0.020) in the low-LA group but hardly changed in the high-ALA group. Nearly all ALA from the plasma phospholipid pool was converted into eicosapentaenoic acid. Conversion of eicosapentaenoic acid into docosapentaenoic acid and docosahexaenoic acid hardly changed in the 3 groups and was <0.1% of dietary ALA. In absolute amounts, it was unchanged in the low-LA group, but increased from 0.7 to 1.9 mg (P = 0.001) in the high-ALA group. ALA oxidation was unchanged by the dietary interventions. The amounts of ALA and LA in the diet, but not their ratio, determine ALA conversion.

Comparison of the conversion rates of α-linolenic acid (18:3( n − 3)) and stearidonic acid (18:4( n − 3)) to longer polyunsaturated fatty acids in rats

The Δ6-desaturase reaction is regarded to be the rate-limiting step in the conversion of linoleic acid (18:2( n − 6)) to arachidonic acid (20:4( n − 6)). The same is probably also the case with the conversion of α-linolenic acid (18:3( n − 3)) to eicosapentaenoic acid (20:5( n − 3)). However, there are very few in vivo studies that directly compare the conversion rate between 18:3( n − 3) and stearidonic acid (18:4( n − 3)), which is the Δ6-desaturated product of 18:3( n − 3). We compared this rate by feeding rats on a lipid-free diet supplemented with lard (9%, w/w) and 18:3( n − 3) ethyl ester (1%) diet or on a diet containing lard (9%) and 18:4( n − 3) ethyl ester (1%). A lard (10%)-supplemented diet was used as the control diet. The fatty acid compositions of total phospholipids, triglycerides and free fatty acids of both liver and plasma were measured after 1 or 3 weeks on different diets. The molar ratio of 20:5( n − 3) of most lipid fractions was about 2-fold higher in rats fed the 18:4( n − 3)-supplemented diet than in rats fed the 18:3( n − 3)-supplemented diet. 18:4( n − 3) was found in the liver lipid fraction in only a very small amount, even in the 18:4( n − 3)-supplemented groups. Thus, desaturation at C-6 is suggested to be the rate-limiting step in the conversion of 18:3( n − 3) to 20:5( n − 3).

Conversion of linseed oil to an eicosapentaenoic acid-containing oil by Mortierella alpina 1S-4 at low temperature

The production of 5,8,11,14,17-cis-eicosapentaenoic acid (EPA) by Mortierella fungi was hgghly stimulated when they were grown in a medium containing linseed oil at low temperature. This phenomenon was suggested to be mainly due to low temperature-dependent production of EPA from arachidonic acid formed through the n-6 route, although conversion of α-linolenic acid in the added linseed oil to EPA through the n-3 route took place at the same time. The amount of EPA accumulated reached 1.88 mg/ml of culture broth (66.6 mg/g dry mycelia) on cultivation of M. alpina 1S-4 with linseed oil at 12° C.