Lymphatic Transport of α-Linolenic Acid and Its Conversion to Long Chain n-3 Fatty Acids in Rats Fed Microemulsions of Linseed Oil

In the present study we evaluated the uptake of ALA and its conversion to EPA + DHA in rats given linseed oil (LSO) in native form or as a microemulsion in whey protein or in lipoid. In a single oral dose study in which rats maintained on rodent pellets deficient in ω-3 fatty acids were intubated with 0.35 g LSO in lipoid, the amount of ALA present in lymph was increased reaching a maximum concentration of 16.23 mg/ml at 2.5 h. The amount of ALA present in lymph was increased to a maximum level of 10.95 mg/ml at 4 h in rats given LSO as a microemulsion in whey protein. When LSO was given without emulsification, the amount of ALA present in lymph was found to reach a maximum level of 7.08 mg/ml at 6 h. A similar result was observed when weaning rats were intubated with 0.15 g of LSO per day for a period of 60 days. Higher levels of ALA by 41 and 103 % were observed in lymph lipids of rats given microemulsions of LSO in whey protein and in lipoid respectively as compared to rats given LSO without pre-emulsification. Very little conversion of ALA to EPA and DHA was observed in lymph lipids but higher amounts of EPA + DHA was observed in liver and serum of rats given LSO in microemulsion form. This study indicated that ALA concentration in lymph lipids was increased when LSO was given in microemulsion form in lipoid and further conversion to EPA and DHA was facilitated in liver and serum.     

Serum n-3 Tetracosapentaenoic Acid and Tetracosahexaenoic Acid Increase Following Higher Dietary α-Linolenic Acid but not Docosahexaenoic Acid

n‐3 Tetracosapentaenoic acid (24:5n‐3, TPAn‐3) and tetracosahexaenoic acid (24:6n‐3, THA) are believed to be important intermediates to docosahexaenoic acid (DHA, 22:6n‐3) synthesis. The purpose of this study is to report for the first time serum concentrations of TPAn‐3 and THA and their response to changing dietary α‐linolenic acid (18:3n‐3, ALA) and DHA. The responses will then be used in an attempt to predict the location of these fatty acids in relation to DHA in the biosynthetic pathway. Male Long Evans rats (n = 6 per group) were fed either a low (0.1% of total fatty acids), medium (3%) or high (10%) ALA diet with no added DHA, or a low (0%), medium (0.2%) or high (2%) DHA diet with a background of 2% ALA for 8 weeks post‐weaning. Serum n‐3 and n‐6 polyunsaturated fatty acid (PUFA) concentrations (nmol/mL ± SEM) were determined by gas chromatography–mass spectrometry. Serum THA increases from low (0.3 ± 0.1) to medium (5.8 ± 0.7) but not from medium to high (4.6 ± 0.9) dietary ALA, while serum TPAn‐3 increases with increasing dietary ALA from 0.09 ± 0.04 to 0.70 ± 0.09 to 1.23 ± 0.14 nmol/mL. Following DHA feeding, neither TPAn‐3 or THA change across all dietary DHA intake levels. Serum TPAn‐3 demonstrates a similar response to dietary DHA. In conclusion, this is the first study to demonstrate that increases in dietary ALA but not DHA increase serum TPAn‐3 and THA in rats, suggesting that both fatty acids are precursors to DHA in the biosynthetic pathway.     

17β-Estradiol Increases Liver and Serum Docosahexaenoic Acid in Mice Fed Varying Levels of α-Linolenic Acid

Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17β-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status.     

n-3 Docosapentaenoic Acid Intake and Relationship with Plasma Long-Chain n-3 Fatty Acid Concentrations in the United States: NHANES 2003–2014

The long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a crucial role in health, but previous National Health and Nutrition Examination Survey (NHANES) analyses have shown that EPA and DHA intake in the United States is far below recommendations (~250–500 mg/day EPA + DHA). Less is known about docosapentaenoic acid (DPA), the metabolic intermediate of EPA and DHA; however, evidence suggests DPA may be an important contributor to long-chain n-3 fatty acid intake and impart unique benefits. We used NHANES 2003–2014 data (n = 45,347) to assess DPA intake and plasma concentrations, as well as the relationship between intake and plasma concentrations of EPA, DPA, and DHA. Mean DPA intake was 22.3 ± 0.8 mg/day from 2013 to 2014, and increased significantly over time (p < 0.001), with the lowest values from 2003 to 2004 (16.2 ± 1.2 mg/day). DPA intake was higher in adults (20–55 years) and seniors (55+ years) compared to younger individuals. In regression analyses, DPA intake was a significant predictor of plasma EPA (β = 138.5; p < 0.001) and DHA (β = 318.9; p < 0.001). Plasma DPA was predicted by EPA and DHA intake (β = 13.15; p = 0.001 and β = 7.4; p = 0.002), but not dietary DPA (p = 0.3). This indicates that DPA intake is not a good marker of plasma DPA status (or vice versa), and further research is needed to understand the factors that affect the interconversion of EPA and DPA. These findings have implications for future long-chain n-3 fatty acids dietary recommendations.     

Fatty Acid Composition of the Maternal Diet During the First or the Second Half of Gestation Influences the Fatty Acid Composition of Sows’ Milk and Plasma,and Plasma of Their Piglets

Dietary supplements of olive oil (OO) or fish oil (FO) during the first (G1: day 1–60) or second half of gestation (G2: day 60 to term, day 115) were offered to pregnant sows. The proportion of fatty acids in milk and plasma were determined by gas chromatography. When supplements were given during G1, the proportions of oleic acid (OA) and arachidonic acid (AA) in the plasma were higher in the OO group than in the FO group, whereas docosahexaenoic acid (DHA) was higher in the latter group at day 56 of gestation. These differences in plasma DHA were still apparent at day 7 of lactation. Similarly, DHA was also higher in the colostrum and milk on days 3 and 21 of lactation and in the plasma of piglets from FO dams compared to the OO group, whereas AA was lower. When the FO supplement was given during G2, AA was lower and DHA higher in the plasma at day 105 of gestation and at day 7 of lactation compared with the OO group. Likewise, DHA was greater in FO than in OO animals during lactation in colostrum and in milk on days 3 and 21 of lactation, and in 3-day old suckling piglets plasma, whereas AA was lower in these animals. Thus, maternal adipose tissue plays an important role in the storage of dietary long-chain polyunsaturated fatty acids (LCPUFA) during G1. They are mobilized around parturition for milk synthesis, and an excess of dietary n-3 LCPUFA decreases the availability of AA in suckling newborns.     

Synergism of α-Linolenic Acid, Conjugated Linoleic Acid and Calcium in Decreasing Adipocyte and Increasing Osteoblast Cell Growth

Whole fat milk and dairy products (although providing more energy compared to low- or non-fat products), are good sources of α-linolenic acid (ALA), conjugated linoleic acid (CLA) and calcium, which may be favorable in modulating bone and adipose tissue metabolism. We examined individual and/or synergistic effects of ALA, CLA and calcium (at levels similar to those in whole milk/dairy products) in regulating bone and adipose cell growth. ST2 stromal, MC3T3-L1 adipocyte-like and MC3T3-E1 osteoblast-like cells were treated with: (a) linoleic acid (LNA):ALA ratios = 1–5:1; (b) individual/combined 80–90 % c9, t11 (9,11) and 5–10 % t10, c12 (10,12) CLA isomers; (c) 0.5–3.0 mM calcium; (d) combinations of (a), (b), (c); and (e) control. Local mediators, including eicosanoids and growth factors, were measured. (a) The optimal effect was found at the 4:1 LNA:ALA ratio where insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) production was the lowest in MC3T3-L1 cells. (b) All CLA isomer blends decreased MC3T3-L1 and increased MC3T3-E1 cell differentiation. (c) 1.5–2.5 mM calcium increased ST2 and MC3T3-E1, and decreased MC3T3-L1 cell proliferation. (d) Combination of 4:1 LNA:ALA + 90:10 % CLA + 2.0 mM calcium lowered MC3T3-L1 and increased MC3T3-E1 cell differentiation. Overall, the optimal LNA:ALA ratio to enhance osteoblastogenesis and inhibit adipogenesis was 4:1. This effect was enhanced by 90:10 % CLA + 2.0 mM calcium, indicating possible synergism of these dietary factors in promoting osteoblast and inhibiting adipocyte differentiation in cell cultures.     

Inhibitory Effect of Conjugated α-Linolenic Acid from Bifidobacteria of Intestinal Origin on SW480 Cancer Cells

In this study, we assessed the ability of six strains of bifidobacteria (previously shown by us to possess the ability to convert linoleic acid to c9, t11-conjugated linoleic acid (CLA) to grow in the presence of α-linolenic acid and to generate conjugated isomers of the fatty acid substrate during fermentation for 42 h. The six strains of bifidobacteria were grown in modified MRS (mMRS) containing α-linolenic acid for 42 h at 37 °C, after which the fatty acid composition of the growth medium was assessed by gas liquid chromatography (GLC). Indeed, following fermentation of one of the strains, namely Bifidobacterium breve NCIMB 702258, in the presence of 0.41 mg/ml α-linolenic acid, 79.1% was converted to the conjugated isomer, C18:3 c9, t11, c15 conjugated α-linolenic acid (CALA). To examine the inhibitory effect of the fermented oils produced, SW480 colon cancer cells were cultured in the presence of the extracted fermented oil (10–50 μg/ml) for 5 days. The data indicate an inhibitory effect on cell growth (p ≤ 0.001) of CALA, with cell numbers reduced by 85% at a concentration of 180 μM, compared with a reduction of only 50% with α-linolenic acid (p ≤ 0.01).     

Increased Elongase 6 and Δ9-Desaturase Activity are Associated with n-7 and n-9 Fatty Acid Changes in Cystic Fibrosis

Patients with cystic fibrosis, caused by mutations in CFTR, exhibit specific and consistent alterations in the levels of particular unsaturated fatty acids compared with healthy controls. Evidence suggests that these changes may play a role in the pathogenesis of this disease. Among these abnormalities are increases in the levels of n-7 and n-9 fatty acids, particularly palmitoleate (16:1n-7), oleate (18:1n-9), and eicosatrienoate or mead acid (20:3n-9). The underlying mechanisms of these particular changes are unknown, but similar changes in the n-3 and n-6 fatty acid families have been correlated with increased expression of fatty acid metabolic enzymes. This study demonstrated that cystic fibrosis cells in culture exhibit increased metabolism along the metabolic pathways leading to 16:1n-7, 18:1n-9, and 20:3n-9 compared with wild-type cells. Furthermore, these changes are accompanied by increased expression of the enzymes that produce these fatty acids, namely Δ5, Δ6, and Δ9 desaturases and elongases 5 and 6. Taken together, these findings suggest that fatty acid abnormalities of the n-7 and n-9 series in cystic fibrosis are as a result, at least in part, of increased expression and activity of these metabolic enzymes in CFTR-mutated cells.     

Tetradecylthioacetic Acid Increases Hepatic Mitochondrial β-Oxidation and Alters Fatty Acid Composition in a Mouse Model of Chronic Inflammation

The administration of tetradecylthioacetic acid (TTA), a hypolipidemic and anti-inflammatory modified bioactive fatty acid, has in several experiments based on high fat diets been shown to improve lipid transport and utilization. It was suggested that increased mitochondrial and peroxisomal fatty acid oxidation in the liver of Wistar rats results in reduced plasma triacylglycerol (TAG) levels. Here we assessed the potential of TTA to prevent tumor necrosis factor (TNF) α-induced lipid modifications in human TNFα (hTNFα) transgenic mice. These mice are characterized by reduced β-oxidation and changed fatty acid composition in the liver. The effect of dietary treatment with TTA on persistent, low-grade hTNFα overexpression in mice showed a beneficial effect through decreasing TAG plasma concentrations and positively affecting saturated and monounsaturated fatty acid proportions in the liver, leading to an increased anti-inflammatory fatty acid index in this group. We also observed an increase of mitochondrial β-oxidation in the livers of TTA treated mice. Concomitantly, there were enhanced plasma levels of carnitine, acetyl carnitine, propionyl carnitine, and octanoyl carnitine, no changed levels in trimethyllysine and palmitoyl carnitine, and a decreased level of the precursor for carnitine, called γ-butyrobetaine. Nevertheless, TTA administration led to increased hepatic TAG levels that warrant further investigations to ascertain that TTA may be a promising candidate for use in the amelioration of inflammatory disorders characterized by changed lipid metabolism due to raised TNFα levels.     

Synthesis and Properties of Lipoamino Acid–Fatty Acid Mixtures: Influence of the Amphiphilic Structure

The acylation of amino acids by acid chlorides with from 8 to 12 carbon atoms in alkaline aqueous medium following Schotten–Baumann reaction results in sodium salts of a N ^α-acylamino acid and fatty acid mixture. The latter are present in a proportion from 40 to 60%. These compositions represent mixtures of amphiphilic anionic surfactants. Together they contribute to the properties of the formulation. Measurements of the surface-active properties of these formulations, such as critical micelle concentration (CMC), surface tension at the CMC (ST), foaming capacity (FC) and foaming stability (FS), show that surfactant mixtures with the longest chain have the most desirable properties. They are comparable to commercial petroleum-based surfactants. Thus, the CMC, ST and CM values of the formulation obtained starting from leucine and dodecanoyl chloride (310 mg/l, 30.1 mN/m and 200%, respectively) are similar to, and even better than, sodium dodecylsulfate (290 mg/l, 39.1 mN/m and 230%, respectively).     

Does Short-Term Dietary Omega-3 Fatty Acid Supplementation Influence Brain Hippocampus Gene Expression of Zinc Transporter-3?

Dietary omega-3 fatty acids have been recognized to improve brain cognitive function. Deficiency leads to dysfunctional zinc metabolism associated with learning and memory impairment. The objective of this study is to explore the effect of short-term dietary omega-3 fatty acids on hippocampus gene expression at the molecular level in relation to spatial recognition memory in mice. A total of 24 male BALB/c mice were randomly divided into four groups and fed a standard pellet as a control group (CTL, n = 6), standard pellet added with 10% (w/w) fish oil (FO, n = 6), 10% (w/w) soybean oil (SO, n = 6) and 10% (w/w) butter (BT, n = 6). After 3 weeks on the treatment diets, spatial-recognition memory was tested on a Y-maze. The hippocampus gene expression was determined using a real-time PCR. The results showed that 3 weeks of dietary omega-3 fatty acid supplementation improved cognitive performance along with the up-regulation of α-synuclein, calmodulin and transthyretin genes expression. In addition, dietary omega-3 fatty acid deficiency increased the level of ZnT3 gene and subsequently reduced cognitive performance in mice. These results indicate that the increased the ZnT3 levels caused by the deficiency of omega-3 fatty acids produced an abnormal zinc metabolism that in turn impaired the brain cognitive performance in mice.     

Role of Liver X Receptor,Insulin and Peroxisome Proliferator Activated Receptor α on in Vivo Desaturase Modulation of Unsaturated Fatty Acid Biosynthesis

We examined the in vivo contribution of insulin, T090137 (T09), agonist of liver X receptor (LXR), fenofibrate, agonist of peroxisome proliferator activated receptor (PPAR-α) and sterol regulatory element binding protein-1c (SREBP-1c) on the unsaturated fatty acid synthesis controlled by Δ6 and Δ5 desaturases, compared with the effects on stearoylcoenzyme A desaturase-1. When possible they were checked at three levels: messenger RNA (mRNA), desaturase protein and enzymatic activity. In control rats, only fenofibrate increased the insulinemia that was maintained by the simultaneous administration of T09, but this increase has no specific effect on desaturase activity. T09 enhanced SREBP-1 in control animals and the mRNAs and activity of the three desaturases in control and type-1 diabetic rats, demonstrating a LXR/SREBP-1-mediated activation independent of insulin. However, simultaneous administration of insulin and T09 to diabetic rats led to a several-fold increase of the mRNAs of the desaturases, suggesting a strong synergic effect between insulin and LXR/retinoic X receptor (RXR). Moreover, this demonstrates the existence of an interaction between unsaturated fatty acids and cholesterol metabolism performed by the insulin/SREBP-1c system and LXR/RXR. PPAR-α also increased the expression and activity of the three desaturases independently of the insulinemia since it was equivalently evoked in streptozotocin diabetic rats. Besides, PPAR-α increased the palmitoylcoenzyme A elongase, evidencing a dual regulation in the fatty acid biosynthesis at the level of desaturases and elongases. The simultaneous administration of fenofibrate and T09 did not show additive effects on the mRNA expression and activity of the desaturases. Therefore, the results indicate a necessary sophisticated interaction of all these factors to produce the physiological effects.     

Lipid Classes and Fatty Acid Patterns are Altered in the Brain of γ-Synuclein Null Mutant Mice

The well-documented link between α-synuclein and the pathology of common human neurodegenerative diseases has increased attention to the synuclein protein family. The involvement of α-synuclein in lipid metabolism in both normal and diseased nervous system has been shown by many research groups. However, the possible involvement of γ-synuclein, a closely-related member of the synuclein family, in these processes has hardly been addressed. In this study, the effect of γ-synuclein deficiency on the lipid composition and fatty acid patterns of individual lipids from two brain regions has been studied using a mouse model. The level of phosphatidylserine (PtdSer) was increased in the midbrain whereas no changes in the relative proportions of membrane polar lipids were observed in the cortex of γ-synuclein-deficient compared to wild-type (WT) mice. In addition, higher levels of docosahexaenoic acid were found in PtdSer and phosphatidylethanolamine (PtdEtn) from the cerebral cortex of γ-synuclein null mutant mice. These findings show that γ-synuclein deficiency leads to alterations in the lipid profile in brain tissues and suggest that this protein, like α-synuclein, might affect neuronal function via modulation of lipid metabolism.     

Effects of doping cations on the densification and microstructure of flash-sintered α-Al2O3

The effects of dopants with different valences on the flash sintering behavior of α-Al₂O₃ are investigated. The results indicate that regardless of their valence and ionic radius, all the tested dopants reduce the onset temperature more effectively compared to undoped Al₂O₃. Interestingly, the relative density and grain size of the flash-sintered samples exhibit an inverse linear relationship. The data for the samples doped with non-trivalent cations fall on a different line than those for the samples doped with trivalent cations and the undoped samples. Dopants have an effect on the flash sintering behavior of Al₂O₃ because flash sintering increases the solubility of the dopants in alumina, creating more point defects, and thereby increasing the electrical conductivity of the material. The mechanisms for point defect generation in trivalent and non-trivalent dopants are different.     

Pro- and Antioxidative Effect of α-Tocopherol on Edible Oils, Triglycerides and Fatty Acids

Using advanced electron paramagnetic resonance techniques (EPR), oxidation of crude vegetable oils and their components (fatty acids and triglycerides) by radicals generated from hydrogen peroxide was investigated. The correlation rotational times were determined allowing us to characterize radicals formed during edible oils oxidation. Additionally ¹H- and ¹⁴N-hyperfine coupling constants differentiate the fatty acids dependently on their unsaturation. The acids with a higher number of unsaturated bonds exhibit higher A_N values of PBN/·lipid adduct. The waste oil with high free fatty acids content underwent the oxidation reaction more efficiently, however due to saturation and the high content of the fatty acids the carbon-centered radicals formed (upon hydrogen peroxide radicals) and their PBN (N-tert-butyl-α-phenylnitrone) adducts were less stable. The antioxidant effect was dependent on the amount of α-tocopherol added. In small amounts of up to 0.35 mg/1 g of fatty acid or triglyceride, it inhibited the creation of PBN/·lipid adducts while with higher amounts it intensified adduct formation. The α-tocopherol (AT) addition influence was also studied as spin scavenging dependence and indicated that any addition of the antioxidant in the investigated samples led to free radical scavenging and the effect increased with the increase in AT content.     

No Effect of Omega-3 Fatty Acid Supplementation on Cognition and Mood in Individuals with Cognitive Impairment and Probable Alzheimer’s Disease: A Randomised Controlled Trial

Findings from epidemiological and observational studies have indicated that diets high in omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may reduce the risk of cognitive decline and Alzheimer’s disease (AD). To determine if increasing intake of DHA and EPA through supplementation is beneficial to cognition and mood in individuals with cognitive impairment no dementia (CIND) or Alzheimer’s disease (AD) a four month, randomised, double-blind, placebo controlled study was conducted. Fifty-seven participants with CIND and nineteen with AD were randomised to receive either omega-3 PUFAs (600 mg EPA and 625 mg DHA per day) or placebo (olive oil) over a four month period. Elevating depleted levels of EPA and DHA through supplementation in individuals with CIND or AD was found to have negligible beneficial effect on their cognition or mood. These findings confirm an overall negligible benefit of omega-3 PUFA supplementation for those with cognitive impairment and dementia. More intervention studies need to be undertaken with longer study durations and larger sample sizes. It may prove fruitful to examine effects of different doses as well as effects in other dementia subtypes.     

Profiling of Fatty Acids Composition in Suet Oil Based on GC–EI-qMS and Chemometrics Analysis

Fatty acid (FA) composition of suet oil (SO) was measured by precolumn methylesterification (PME) optimized using a Box–Behnken design (BBD) and gas chromatography/electron ionization-quadrupole mass spectrometry (GC–EI-qMS). A spectral library (NIST 08) and standard compounds were used to identify FAs in SO representing 90.89% of the total peak area. The ten most abundant FAs were derivatized into FA methyl esters (FAMEs) and quantified by GC–EI-qMS; the correlation coefficient of each FAME was 0.999 and the lowest concentration quantified was 0.01 μg/mL. The range of recovery of the FAMEs was 82.1%–98.7% (relative standard deviation 2.2%–6.8%). The limits of quantification (LOQ) were 1.25–5.95 μg/L. The number of carbon atoms in the FAs identified ranged from 12 to 20; hexadecanoic and octadecanoic acids were the most abundant. Eighteen samples of SO purchased from Qinghai, Anhui and Jiangsu provinces of China were categorized into three groups by principal component analysis (PCA) according to the contents of the most abundant FAs. The results showed SOs samples were rich in FAs with significantly different profiles from different origins. The method described here can be used for quality control and SO differentiation on the basis of the FA profile.     

Facet Effects of α-Fe2O3 with Different Morphologies on the Thermal Decomposition of Ammonium Erchlorate

Catalysis Letters - Hematite α-Fe2O3 with microrods and nanoparticles, corresponding to the predominantly exposed (110) and (104) facets, respectively, were prepared using a...