Cis-polyunsaturated Fatty Acids Research Articles

Association of dietary fatty acids with the risk of atherosclerotic cardiovascular disease in a prospective cohort of United States veterans

BackgroundAtherosclerotic cardiovascular diseases (ASCVDs) are the leading cause of worldwide adult mortality. Although broad classes of dietary fats have been shown to alter ASCVD risk, the roles that individual dietary fatty acids play in influencing ASCVD risk are unclear. ObjectivesThe aim of this prospective cohort study was to examine the relationships of the total fat classes and individual fatty acids with the risk of ASCVD. MethodsThe Million Veteran Program is a prospective cohort whereby dietary intake of fatty acids was assessed in 158,198 participants that had enrolled between January 2011 and November 2018 and were free of ASCVD at baseline. Incident ASCVD was ascertained from the Veterans Affairs electronic health records and the National Death Index. Multivariable-adjusted hazard ratios (HRs) for the relationship between fat intake and ASCVD risk were computed using Cox regression models. ResultsThe mean age was 61 years, 88% were males. A total of 11,771 ASCVD events were identified during the follow-up. When compared with the lowest quintile, participants in the highest quintile of dietary trans-monounsaturated fats and conjugated linoleic acids had an increased risk (HR [95% CI]) of ASCVD events: 1.10 (1.04, 1.17) and 1.11 (1.05, 1.18), respectively. When compared with low consumers, participants in the highest quintile of total cis-polyunsaturated fatty acid intake had a lower risk of experiencing an ASCVD event 0.93 (0.87, 0.99). ConclusionAlthough higher intakes of specific trans-fatty acids and conjugated linoleic were associated with an increased risk of ASCVD, the same cannot be said for all other fat classes. This work suggests that care must be taken when drawing general conclusions regarding the health effects of dietary individual fatty acids.

Longer-term soy nut consumption improves vascular function and cardiometabolic risk markers in older adults: Results of a randomized, controlled cross-over trial

Soy foods may contribute to the beneficial health effects of healthy plant-based diets on the risk to develop cardiovascular disease (CVD). However, their effects on vascular function have hardly been studied. To investigate longer-term effects of soy nut consumption on vascular function and cardiometabolic risk markers in healthy older men and women. Twenty-three healthy participants (age: 60-70 years; BMI: 20-30kg/m2) participated in a randomized, controlled, single-blinded cross-over trial with an intervention (67g/day of soy nuts providing 25.5g protein and 174mg isoflavones) and control period (no nuts) of 16 weeks, separated by eight weeks wash-out. Adults followed the Dutch food-based dietary guidelines. No serious adverse events were reported and the soy nut regime was well tolerated. Body weights remained stable during the whole study. A higher protein (3.1 energy percent [En%]) and a lower carbohydrate intake (2.0 En%) was observed during the intervention period. Total fat intake was comparable, but that of saturated (-1.3 En%), cis-monounsaturated (-1.5 En%) and cis-polyunsaturated fatty acids (+1.9 En%) differed. Serum isoflavone concentrations were higher after the intervention as compared with the control period (daidzein: 127.8ng/mL; 95% CI: 74.3-181.3ng/mL; p<0.001 and genistein: 454.2ng/mL; 95% CI: 266.6-641.8ng/mL; p<0.001). Brachial artery flow-mediated vasodilation was 1.48 percent points (pp; 95% CI: 0.08-2.89 pp; p=0.040) higher following soy nut intake. The carotid artery reactivity response and arterial stiffness did not differ. Serum LDL-cholesterol was lower (0.17mmol/L; 95% CI: 0.02-0.32mmol/L; p=0.027), while HDL-cholesterol and triacylglycerol concentrations were comparable. Mean arterial pressure (MAP) was lower (3mmHg; 95% CI: 0-6mmHg; p=0.035). Longer-term soy nut intake as part of a healthy diet improved endothelial function, LDL-cholesterol concentrations and MAP levels, suggesting mechanisms by which an increased soy food intake beneficially affects CVD risk in older adults. Registered under ClinicalTrials.gov Identifier no. NCT03627637.

Basal diets with different starch contents do not modify the metabolism of ricinoleic acid in dairy goats

The aims of this study are to evaluate the effects of basal diets and inclusion or not of oil blend on dry matter (DM) and fatty acid (FA) intake, milk yield and FA profile, and metabolism of ricinoleic acid. Eight dairy goats in early lactation (body weight, 40.78 ± 5.14 kg; milk yield, 1.02 ± 0.34 kg/day; days in milk, 27.5 ± 2.25) were assigned to a replicated 4 × 4 Latin square design in a 2 × 2 factorial arrangement with two carbohydrate sources (ground corn or citrus pulp) and with or without castor and sunflower oil blend inclusion (20 g/kg of DM). The DM intake (DMI), milk yield, and composition were not affected by the experimental diets (P > 0.05). Goats fed citrus pulp diets containing oil blend had higher 12OH,c9−18:1 intake (P = 0.035). The milk of the goats fed ground corn or blend oil contained higher concentrations of t11−18:1 and c9t11−18:2. The oxo-FA and hydroxy-FA which are ricinoleic acid and derived (RADFA) were detected only in milk of goats fed oil blend and the concentration was approximately 35 mg/g of total FA. The 12OH,c9−18:1 concentration in milk of goats fed the oil blend was approximately 2 % of RADFA, whereas the concentration of 12oxo-18:0 was approximately 67 % of RADFA. The 8-oxo-14:0, 10-oxo-16:0, 12OH-18:0, and the total RADFA concentrations tended to be higher (P < 0.10) in milk of goats fed oil blend with citrus pulp. The contents of short and medium-chain fatty acids (SMCFA), branched-chain fatty acids (BCFA), and saturated fatty acids (SFA) were lower (P < 0.05) in the milk of the goats fed oil blend diets. The total cis-polyunsaturated fatty acids (cis-PUFA) was higher (P = 0.004) in the milk of the goats fed ground corn and was not affected by oil addition. The estimated melting point of the milk of the goats fed the oil blend (37.1 °C) was higher (P = 0.013) than the milk of goats that were not fed the oil blend (36.7 °C). In conclusion, diets based on ground corn or citrus pulp do not influence the metabolism of ricinoleic acid. Castor oil blend may be a strategy to enhance milk with bioactive fatty acids such as conjugated linoleic acid (CLA) and RADFA, without affecting its melting point.

Comparative Nutrient Profiling of Retail Goat and Cow Milk.

Goat milk is globally consumed but nutritional profiling at retail level is scarce. This study compared the nutrient composition of retail cow and goat milk (basic solids, fatty acids, minerals, and phytoestrogens) throughout the year and quantified the potential implications on the consumers’ nutrient intakes. When compared to cow milk, goat milk demonstrated nutritionally desirable traits, such as lower concentrations of C12:0, C14:0, C16:0 and Na: K ratio, and the higher concentrations of cis polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), isoflavones, B, Cu, Mg, Mn, P and I, although the latter may be less desirable in cases of high milk intakes. However, in contrast with nutritional targets, it had lower concentrations of omega-3 PUFA, vaccenic acid, lignans, Ca, S and Zn. The extent of these differences was strongly influenced by season and may demonstrate a combination of differences on intrinsic species metabolism, and farm breeding/husbandry practices.

FATTY ACID COMPOSTION OF SELECTED VIETNAMESE BISCUITES INCLUDING TRANS-ISOMERS

In this study, fatty acid compositions including trans-isomers contents of selected Biscuits products produced by Vietnamese confectionery companies and imported products purchased from Hanoi markets were determined by gas chromatography. Palmitic acid and oleic acid were the most abundant, with concentrations ranged from 21 % to 52 %, and 23 % to 43 %, respectively, and followed by linoleic acid, lauric acid, myristic acid. The saturated, cis-monounsaturated and cis-polyunsaturated fatty acid contents were within ranges of 37 % - 75 %, 18 % - 43 %, 0.4 – 26 % of total fatty acid methyl ester, respectively. Trans-fatty acids were identified in all samples excepted brands B3, B13, B17, B24*, and the contents ranged from 0.07 % to 7,16 %. A considerable variability in fatty acid composition of biscuits which indicated that different types of fats and oils were used for production of selected Vietnamese biscuits and imported products was showed by these results got from the study.

A novel series of C18–C22 trans ω3 PUFA from Northern and Southern Hemisphere strains of the marine haptophyte Imantonia rotunda

A series of novel C18–C22trans ω3 polyunsaturated fatty acids (PUFA) with a single trans double bond in the ω3 position was found in Northern and Southern Hemisphere strains of the marine haptophyte Imantonia rotunda. The novel ω3 PUFA were identified as 18:3(9c,12c,15t) (0.2–1.8 % of total fatty acids), 18:4(6c,9c,12c,15t) (1.9–4.1 %), 18:5 (3c,6c,9c,12c,15t) (0.7–8.8 %), 20:5(5c,8c,11c,14c,17t) (1.2–4.1 %) and 22:6(4c,7c,10c,13c,16c,19t) (0.3–4.3 %), and were accompanied by larger proportions of the all cis isomers: 18:3ω3(9,12,15) (2.7–3.5 %), 18:4ω3(6,9,12,15) (9.3–14.3 %), 18:5ω3(3,6,9,12,15) (7.8–18.5 %), 20:5ω3(5,8,11,14,17) (3.2–3.9 %), 22:5ω3(7,10,13,16,19) (0.1–0.3 %) and 22:6ω3(4,7,10,13,16,19) (2.3–5.2 %). GC analysis of FAME using a non-polar column did not reveal the trans isomers as they coeluted with the all cis PUFA. However, GC using a polar column resolved the trans PUFA from the all cis PUFA, with the trans isomers eluting before the all cis isomers. GC-MS of FAME fractionated by argentation solid-phase chromatography confirmed the molecular ions of all components. FAME were derivatized to form 4,4-dimethyloxazoline (DMOX) derivatives, and GC-MS revealed the same double bond positions for each trans and cis FAME. The results suggest that the ω3 trans double bond originated from the Δ15/ω3 desaturation of 18:2(9c,12c), suggesting that this desaturase has dual cis/trans activity in these species. These results indicate that 18:3(9c,12c,15 t) was the precursor trans isomer produced for the trans series and further desaturation by the common Δ6 desaturase to produce the trans tetraene and successive elongations and desaturations led to the subsequent series of trans ω3 PUFA isomers. To our knowledge, this is the first report of these trans ω3 isomers occurring in strains of I. rotunda. These trans ω3 PUFA may be used as biomarkers in marine food webs for this species and with their unique structure may be biologically active.

Effect of Natural Additives on the Fatty Acid Signatures of Green Mussel P erna viridis L. in a Time-Dependent Accelerated Shelf Life Study

The present study identified the freeze-dried concentrate of green mussel to possess valuable nutritional properties with respect to long-chain polyunsaturated fatty acids. The freeze-dried concentrate (C0) was stabilized with different ratios of naturally derived antioxidative oleoresins of Rosmarinus officinalis and Curcuma longa along with trace amounts of other natural additives to obtain four combinations (C1, C2, C3 and C4) and was subjected to accelerated shelf storage for 90 days (d90) to understand their role in retaining the desired nutritional composition. A threshold level of oleoresins of C. longa : R. officinalis (0.8:0.4%) was sufficient for optimum antioxidant activity, and further addition of endogenous antioxidants did have negative impacts on stability of the polyunsaturated fatty acid compositions of the green mussel concentrate. The combinations C2 and C4 effectively arrested the isomeric conversion of cis polyunsaturated fatty acids to their trans conformers at d0 and d90 than recorded in C0. Practical Applications The nonconjugated olefinic system in the long-chain polyunsaturated fatty acids in the marine products make them susceptible to oxidation, limiting the amount of time that such products can be stored on the shelf. The use of natural oleoresins in meat products and fried foods has been extensively researched and used in commercialized foods. The present work focused to study the use of natural antioxidative additives in increasing the shelf life of the freeze-dried concentrate developed from green mussel Perna viridis and to retain the native form of unsaturated fatty acids, which are highly susceptible to oxidation. The study demonstrated that a combination of green mussel concentrate rich in long-chain polyunsaturated fatty acids and naturally derived antioxidative substances might result in nutritionally valuable functional food products.

Arachidonic acid promotes migration and invasion through a PI3K/Akt-dependent pathway in MDA-MB-231 breast cancer cells

Arachidonic acid (AA) is a common dietary n−6 cis polyunsaturated fatty acid that under physiological conditions is present in an esterified form in cell membrane phospholipids, however it might be present in the extracellular microenvironment. AA and its metabolites mediate FAK activation, adhesion and migration in MDA-MB-231 breast cancer cells. However, it remains to be investigated whether AA promotes invasion and the signal transduction pathways involved in migration and invasion. Here, we demonstrate that AA induces Akt2 activation and invasion in MDA-MB-231 cells. Akt2 activation requires the activity of Src, EGFR, and PIK3, whereas migration and invasion require Akt, PI3K, EGFR and metalloproteinases activity. Moreover, AA also induces NFκB-DNA binding activity through a PI3K and Akt-dependent pathway. Our findings demonstrate, for the first time, that Akt/PI3K and EGFR pathways mediate migration and invasion induced by AA in MDA-MB-231 breast cancer cells.

Dietary fatty acids and cardiovascular disease

In 1991, the Committee on Medical Aspects of Food Policy produced a report on the dietary reference values for food energy and nutrients for groups of people in the United Kingdom. The resulting recommendations, which included specific limits for intakes of total, saturated, trans- and cis-polyunsaturated fatty acids (PUFA) have remained a cornerstone of public health policy ever since, and similar recommendations have been adopted by the World Health Organization. These recommendations were made largely on the basis of specific effects of these fatty acids on the risk of developing atherosclerotic cardiovascular disease (CVD). The intervening years have seen a plethora of human epidemiological and intervention trials to further elucidate the specific relationship between dietary fatty acid intake, plasma lipids and lipoproteins and cardiovascular morbidity and mortality. A number of recent meta-analyses and systematic reviews have revisited the role of specific dietary fatty acid classes and CVD risk. In general, these continue to support a link between saturated fatty acids (SFA) and CVD morbidity/mortality. They also highlight the potent adverse effects of trans fatty acids derived from partially hydrogenated vegetable oil. The most recent data suggest that replacing SFA with cis-PUFA (primarily linoleic acid) has the greatest impact on reducing CVD risk. Evidence of specific beneficial effects of n-3 PUFA is generally stronger for secondary, rather than primary, CVD risk, and it is restricted to very long chain fatty acids of marine origin as opposed to alpha-linolenic acid. Taken together, these data suggest that recent focus on dietary n-6-to-n-3 PUFA ratios may have been misguided, and that future strategies should focus on replacing dietary SFA with total PUFA, rather than concentrating on n-6 : n-3 PUFA ratio.

Arachidonic acid induces an increase of β‐1,4‐galactosyltransferase I expression in MDA‐MB‐231 breast cancer cells

Arachidonic acid (AA) is a common dietary n-6 cis polyunsaturated fatty acid that under physiological conditions is present in an esterified form in cell membrane phospholipids, and it might be present in the extracellular microenvironment. AA and its metabolites are implicated in FAK activation and cell migration in MDA-MB-231 breast cancer cells, and an epithelial-to-mesenchymal-like transition process in mammary non-tumorigenic epithelial cells MCF10A. During malignant transformation is present an altered expression of glycosiltransferases, which promote changes on the glycosilation of cell-surface proteins. The β-1,4-galactosyltransferase I (GalT I) is an enzyme that participates in a variety of biological functions including cell growth, migration, and spreading. However, the participation of AA in the regulation of GalT I expression and the role of this enzyme in the cell adhesion process in breast cancer cells remains to be investigated. In the present study, we demonstrate that AA induces an increase of GalT I expression through a PLA2α, Src, ERK1/2, and LOXs activities-dependent pathway in MDA-MB-231 breast cancer cells. Moreover, MDA-MB-231 cells adhere to laminin via GalT I expression and pretreatment of cells with AA induces an increase of cell adhesion to laminin. In conclusion, our findings demonstrate, for the first time, that AA promotes an increase of GalT I expression through an AA metabolism, Src and ERK1/2 activities-dependent pathway, and that GalT I plays a pivotal role in cell adhesion to laminin in MDA-MB-231 breast cancer cells.

OS091. The origin of preeclampsia in diet-induced maternal endothelial stiffness

Despite research documenting variances in cellular hypoxia, angiogenesis, oxidative stress, endothelial signaling, and autoimmunity, the etiology of preeclampsia remains unknown. Women affected by preeclampsia show increased arterial stiffness and abnormal serum lipids when compared to unaffected mothers. Although enzymes modify and synthesize lipids, most acyl chains are incorporated into cell membranes unmodified from the form in which they were absorbed from the gastrointestinal tract. Therefore, diet plays a major role in determining the rheology and composition of cell membranes. A-To present a model of how diet might alter cell membrane composition and cause increased maternal membrane viscosity when lipids are actively transported across the placenta to the fetus. B-To demonstrate how rapidly changing maternal membrane composition and viscosity might cause the pathological elements of preeclampsia. Literature search. Compared to diets of 10,000 years ago, modern diets have increased trans- and long-chain fatty acids, elevated omega-6 to -3 fatty acid ratios, and produce stiffer cell membranes, therefore might require increased membrane softening components such as cis-polyunsaturated fatty acids (PUFA) to maintain homeoviscosity. High fetal requirements for essential PUFAs might deplete body stores of these molecules in mothers with decreased dietary intake, thereby causing increased maternal membrane stiffness. Native proteins are only marginally stable under physiological conditions. A 2005 study using artificial membranes and the receptor rhodopsin, demonstrated that alteration of membrane lipid composition to increase membrane stiffness caused lower rhodopsin activation [1]. Increased membrane stiffness arising from dietary lipid variances might alter membrane proteins and cause the endothelial signaling dysfunction of preeclampsia. Although primary amino acid sequences remain unchanged, the disruption of tertiary protein structure might yield proteins that appear foreign and thus evoke an immune response, giving rise to antibodies such as agonistic autoantibody angiotensin-1. In mitochondria, disruption of electron transport protein structures might interfere with electron tunneling and increase the production of free radicals and oxidative stress. Because oxygen diffuses more rapidly through flexible versus stiff membranes,stiff cell membranes might initiate the signaling cascade indicative of cellular hypoxia in preeclampsia with increased hypoxia inducible factor and angiogenic factors such as soluble endoglin and fms-like tyrosine kinase. The arterial intima acts as a sensor with blood pressure homeostatic responses modulated by the flexibility of endothelial membranes. Similarly to a diaphragm pressure transducer, if the diaphragm material is stiff, the signal is attenuated; conversely, a flexible diaphragm makes the instrument more sensitive to pressure. Thus, stiffened endothelium might cause hypertension. This paper presents a unifying molecular and cell membrane-based model of how diet-induced maternal cell membrane stiffness offers a coherent and unifying explanation for the pathological changes seen in preeclampsia.

Fatty acid composition including trans isomers of Serbian biscuits

An experimental study was carried out with the aim of evaluating the quality of the lipid fraction of Serbian biscuits. Total fat contents of the biscuit samples ranged between 10.2% and 24.5%. The saturated, cis-monounsaturated and cis-polyunsaturated fatty acid contents were within the ranges of 18.585.6%, 10.649.9% and 2.713.3% of total fatty acids, respectively. The content of trans fatty acids (TFA) ranged from 0.0% to 42.5% and the mean was 10.2%. In a total of 34 investigated samples, 10 of them were found to be trans - free, 8 contained low level of TFA (under 2%), 4 samples contained between 2 and 10% of TFA, while 12 samples contained very high amounts of TFA (12.042.5%). The results obtained showed a considerable variability in fatty acid composition of biscuits which indicated that different types of fats and oils were used for production of biscuits in Serbia.

Lysine 63-linked ubiquitination is important for arachidonic acid-induced cellular adhesion and migration

Arachidonic acid, a dietary cis-polyunsaturated fatty acid, stimulates adhesion and migration of human cancer cells on the extracellular matrix by activation of intracellular signaling pathways. Polyubiquitin chains bearing linkages through different lysine residues convey distinct structural and functional information that is important for signal transduction. We investigated whether ubiquitination was required for arachidonic acid-induced cellular adhesion and migration of MDA-MB-435 cells on collagen type IV. An E1 (ubiquitin-activating enzyme) inhibitor, PYR-431, completely abrogated arachidonic acid-stimulated adhesion. Additionally, expression of a lysine null mutant ubiquitin prevented activation of cellular adhesion. Cells expressing ubiquitin in which lysine 63 (K63) was mutated to arginine (K63R) were unable to adhere to collagen upon exposure to arachidonic acid. When K63 was the only lysine present, the cells retained the ability to adhere, indicating that K63-linked ubiquitin is both necessary and sufficient. Moreover, K63-linked ubiquitin was required for the induction of cell migration by arachidonic acid. The ubiquitin mutants and PYR-431 did not prevent arachidonic acid-induced phosphorylation of TGF-β activated kinase-1 (TAK1) and p38 MAPK, suggesting K63-linked ubiquitination occurs downstream of MAPK. These novel findings are the first to demonstrate a role for K63-linked ubiquitination in promoting cell adhesion and migration.

Health effects of trans-fatty acids: experimental and observational evidence

Growing evidence indicates that trans-fatty acids (TFA) adversely affect cardiovascular health. As part of the World Health Organization (WHO) Scientific Update on TFA, we reviewed the evidence for effects of TFA consumption on coronary heart disease (CHD). We searched Medline publications examining TFA consumption and CHD risk factors or outcomes, emphasizing results of studies in humans. We evaluated and synthesized evidence from both controlled feeding trials evaluating risk factors and long-term observational studies evaluating risk factors or clinical outcomes, each of which have complementary strengths and limitations, to enable the most robust and reliable inferences of effects. The effects of TFA consumption on risk factors most consistently seen in both controlled trials and observational studies included adverse lipid effects (for example [upward arrow] low-density lipoprotein cholesterol, [downward arrow] high-density lipoprotein cholesterol (HDL-C), [upward arrow] total/HDL-C ratio), proinflammatory effects (for example [upward arrow] tumor necrosis factor-alpha activity, [upward arrow] interleukin-6, [upward arrow] C-reactive protein) and endothelial dysfunction. These effects were most prominent in comparison with cis unsaturated fats; adverse effects on total/HDL-C and endothelial function were also seen in comparison with saturated fatty acids (SFA). TFA may also worsen insulin sensitivity, particularly among individuals predisposed to insulin resistance; possible effects on weight gain and diabetes incidence require further confirmation. Five retrospective case-control studies and four prospective cohort studies demonstrated positive associations between TFA consumption and CHD events. A meta-analysis of prospective studies indicated 24, 20, 27 and 32% higher risk of myocardial infarction (MI) or CHD death for every 2% energy of TFA consumption isocalorically replacing carbohydrate, SFA, cis monounsaturated fatty acids and cis polyunsaturated fatty acids, respectively. The differential effects of specific TFA isomers may be important but are less well established. The available evidence indicates that trans-18:1 and particularly trans-18:2 isomers have stronger CHD effects than trans-16:1 isomers. The limited data suggest that the experimental effects of ruminant and industrial TFA are similar when consumed in similar quantities, but very few persons consume such high levels of ruminant TFA, and observational studies do not support adverse CHD effects of ruminant TFA in amounts actually consumed. Controlled trials and observational studies provide concordant evidence that consumption of TFA from partially hydrogenated oils adversely affects multiple cardiovascular risk factors and contributes significantly to increased risk of CHD events. The public health implications of ruminant TFA consumption appear much more limited. The effects of specific TFA isomers require further investigation.

Quantitative effects on cardiovascular risk factors and coronary heart disease risk of replacing partially hydrogenated vegetable oils with other fats and oils

Reduced consumption of trans-fatty acids (TFA) is desirable to lower coronary heart disease (CHD) risk. In practice, partially hydrogenated vegetable oils (PHVO) that contain both TFAs and other fatty acids are the unit of replacement and could be replaced with diverse alternative fats and oils. We performed quantitative estimates of CHD effects if a person's PHVO consumption were to be replaced with alternative fats and oils based on (1) randomized dietary trials and (2) prospective observational studies. We performed meta-analyses of (1) the effects of TFAs on blood lipids and lipoproteins in controlled dietary trials and (2) associations of habitual TFA consumption with CHD outcomes in prospective cohort studies. On the basis of these results and corresponding findings for saturated fatty acids (SFA), cis-monounsaturated fatty acids (MUFA) and cis-polyunsaturated fatty acids (PUFA), we calculated the effects on CHD risk for replacing 7.5% of energy from three different PHVO formulations (containing 20, 35 or 45% TFAs) with butter, lard, palm or vegetable oils. In controlled trials, each 1% energy replacement of TFAs with SFAs, MUFAs or PUFAs, respectively, decreased the total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio by 0.31, 0.54 and 0.67; the apolipoprotein (Apo)-B/ApoAI ratio by 0.007, 0.010 and 0.011; and lipoprotein (Lp)(a) by 3.76, 1.39 and 1.11 mg/l (P<0.05 for each). We also included possible effects on C-reactive protein (CRP) of TFAs vs other fats from one trial. On the basis of these risk factor changes in controlled trials, CHD risk would be variably decreased by different fats and oils replacing 7.5% of energy from 20% TFA PHVO (CHD risk reduction: -2.7% (butter) to -9.9% (canola)); 35% TFA PHVO (-11.9% (butter) to -16.0% (canola)); or 45% TFA PHVO (-17.6% (butter) to -19.8% (canola)). In prospective cohort studies, each 2% energy replacement of TFAs with SFAs, MUFAs or PUFAs would lower CHD risk by 17% (95% confidence interval (CI)=7-25%), 21% (95% CI=12-30%) or 24% (95% CI=15-33%), respectively. On the basis of these associations in observational studies, CHD risk would be variably decreased by different fats and oils replacing 7.5% of energy from 20% TFA PHVO (CHD risk reduction: +0.5% (butter) to -21.8% (soybean)); 35% TFA PHVO (-14.4% (butter) to -33.4% (soybean)); or 45% TFA PHVO (-22.4% (butter) to -39.6% (soybean)). The demonstrated effects on TC/HDL-C, ApoB/ApoAI, Lp(a), and CRP in randomized feeding trials together accounted for approximately 65-80% and approximately 50% of the estimated risk reduction for replacing PHVO with animal fats and vegetable oils, respectively, that would be calculated from prospective cohort studies. Effects on CHD risk of removing PHVO from a person's diet vary depending on the TFA content of the PHVO and the fatty acid composition of the replacement fat or oil, with direct implications for reformulation of individual food products. Accounting for the summed effects of TFAs on multiple CHD risk factors provides more accurate estimates of potential risk reduction than considering each risk factor in isolation, and approaches the estimated risk reduction derived from prospective cohort studies.

Cardiovascular diseases and red meat

Cardiovascular diseases and red meat

Adhesion Receptors Mediate Efficient Non-viral Gene Delivery

For a variety of reasons, including production limitations, potential unanticipated side effects, and an immunological response upon repeated systemic administration, virus-based vectors are as yet not ideal gene delivery vehicles, justifying further research into alternatives. Unlike viral vectors, non-viral vectors pose minimal health risks, but to meet therapeutic requirements their efficacy needs major improvement. This goal may be accomplished by better defining the mechanism of non-viral gene delivery and exploiting specific cellular properties. Here we demonstrate that transfection of epithelial cells with lipoplexes is almost exclusively mediated by the beta1 integrin cell surface receptor. More important, we show that in general, adhesion receptors can be exploited by lipoplexes to gain access to cells, including difficult-to-transfect primary neural stem cells and suspension cells, thereby leading to productive transfection. We propose that adhesion receptors serve as "natural" receptors for lipoplexes. As no natural cellular receptors for lipoplexes have previously been identified, our results are an important step forward in understanding the mechanisms of non-viral gene delivery. Moreover, the finding that adhesion receptors mediate efficient non-viral gene delivery paves the way for the optimization of (standard) transfection procedures as well as ex vivo gene therapy protocols using non-viral vectors.

Folded and Unfolded Conformations of the ω-3 Polyunsaturated Fatty Acid Family: CH3CH2[CHCHCH2]B[CH2]MCOOH. First Principles Study

Polyunsaturated fatty acids (PUFA) like stearidonic acid (SDA;18:4 n-3) eicosapentaenoic acid (EPA; 20:5 n-3), and docosahexaenoic acid (DHA; 22:6 n-3) and its chain fragment models were studied at B3LYP/6-31G(d) levels of theory. Significant conformations for the cis and trans isomers were selected to obtained the thermodynamic functions (DeltaH, DeltaS, DeltaG) for the cis-trans isomerization and for folding using the B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d) level of theory. The structural analysis shows that there are significant differences in thermodynamic function of the trans- and cis-PUFAs. The trans-cis isomerization energy values reinforce the consistency and the relative accuracy of theoretical model calculations. The observed flexibility of naturally cis PUFAs could be explained by a very special "smooth basin" PES of the motif of sp(2)-sp(3)-sp(2) hybrid states as reported previously (J. Phys. Chem. A 2005, 109, 520-533). We assumed that intrinsic thermodynamic functions may describe this flexible folding process. The folding enthalpy as well as the folding entropy suggests that there is a new role of the cis-PUFAs in membranes: these cis isomers may have a strong influence on membrane stability and permeability. The average length of the cis helix and beta PUFA was approximated. The difference between the lengths of these two structures is approximately 10 A.

FATTY ACID COMPOSITION OF DIFFERENT MARGARINES AND BUTTERS FROM PAKISTAN WITH SPECIAL EMPHASIS ON TRANS UNSATURATED CONTENTS

ABSTRACT Fatty acid (FA) composition and isomeric trans unsaturated contents in selected brands of margarines and butter, which are more popular among general consumers of Pakistan, has been reported in this study. A sum of 10 butter and 10 margarine samples, collected from different bakers, confectioners and retail outlets, was analyzed. FA methyl esters were prepared, and quantitative measurements were made using a methyl lignoserate‐coated stationary phase, capillary column (SP‐2340, 60 m × 0.25 mm, 0.20 μm), with flame ionization detection. The contents of saturated FA, cis monounsaturated FA and cis polyunsaturated FA were in the following ranges: margarines 38.9–53.1, 21.9–35.8, 7.45–21.5% and butter 63.7–68.5, 23.0–27.0 and 1.20–2.94%, respectively. Results showed significantly higher amounts of trans FA (TFA) in margarines ranged from 2.45 to 21.1%, whereas butter samples contained less than 5.00% of TFA.

15(S)-Lipoxygenase-2 Mediates Arachidonic Acid-stimulated Adhesion of Human Breast Carcinoma Cells through the Activation of TAK1, MKK6, and p38 MAPK

The dietary cis-polyunsaturated fatty acid, arachidonic acid, stimulates adhesion of metastatic human breast carcinoma cells (MDA-MB-435) to the extracellular matrix, but the molecular mechanisms by which fatty acids modify the behavior of these cells are unclear. Exposure to arachidonic acid activates multiple signaling pathways. Activation of p38 mitogen-activated protein kinase (p38 MAPK) is required for increased cell adhesion to type IV collagen, and this activation is sensitive to inhibitors of lipoxygenases, suggesting a requirement for arachidonic acid metabolism. The goals of the current study were to identify the one or more key metabolites of arachidonic acid that are responsible for activation of p38 MAPK and to elucidate the upstream kinases that lead to p38 MAPK activation. High performance liquid chromatographic analysis revealed that MDA-MB-435 cells metabolize exogenous arachidonic acid predominantly to 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE). Immunoblot analysis with antibodies specific to 15(S)-lipoxygenase-1 (LOX-1) and 15(S)-lipoxygenase-2 (LOX-2) demonstrated the expression of 15-LOX-2, but not 15-LOX-1, in these tumor cells. A LOX inhibitor, nordihydroguaiaretic acid, attenuated production of 15(S)-HETE and inhibited the phosphorylation of p38 MAPK following exposure to arachidonic acid. In contrast, overexpression of LOX-2 sensitized the cells to the addition of arachidonic acid, leading to increased activation of p38 MAPK. Addition of exogenous 15(S)-HETE to MDA-MB-435 cells stimulated cell adhesion to type IV collagen and activated the p38 MAPK pathway, including the upstream kinases transforming growth factor-beta1-activated protein kinase-1 (TAK1) and MAPK kinase 6. Transfection of these cells with a dominant negative form of TAK1 blocked arachidonic acid-stimulated p38 MAPK phosphorylation. These data demonstrate that 15(S)-LOX-2 generation of 15(S)-HETE activates specific growth factor receptor-related signaling pathways, thereby initiating signal transduction events leading to increased cell adhesion to the extracellular matrix.