Meal fatty acids and postprandial vascular reactivity

With increasing recognition of the pivotal role of vascular dysfunction in the progression of atherosclerosis, the vasculature has emerged as an important target for dietary therapies. Recent studies have indicated that chronic fatty acid manipulation alters vascular reactivity, when measured after an overnight fast. However, individuals spend a large proportion of the day in the postprandial (non-fasted) state. Several studies have shown that high fat meals can impair endothelial function within 3-4 h, a time period often associated with peak postprandial lipaemia. Although the impact of meal fatty acids on the magnitude and duration of the postprandial lipaemic response has been extensively studied, very little is known about their impact on vascular reactivity after a meal.

Changes in free amino acids and sugars in potatoes due to sulfate fertilization and the effect on acrylamide formation

To examine how sulfur deprivation may affect acrylamide formation in cooked potatoes, three varieties of potato were grown under conditions of either severe sulfur deprivation or an adequate supply of sulfur. In all three varieties sulfur deprivation led to a decrease in acrylamide formation, even though the levels of sugars, which are acrylamide precursors, were higher in tubers of the sulfur-deprived plants. In one variety the concentration of free asparagine, the other precursor for acrylamide, was also higher. There was a very close correlation between the concentration of asparagine in the tubers expressed as a proportion of the total free amino acid pool and the formation of acrylamide upon cooking, whereas sugars were poorly correlated with acrylamide. In potatoes, where concentrations of sugars are usually limiting, competition between asparagine and other amino acids participating in the Maillard reaction may be a key determinant of the amount of acrylamide that is formed during processing.

Omega-3 polyunsaturated fatty acids and human health outcomes

Current intakes of very long chain omega-3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DNA) are low in most individuals living in Western countries. A good natural source of these fatty acids is seafood, especially oily fish. Fish oil capsules contain these fatty acids too. Very long chain w-3 fatty acids are readily incorporated from capsules into transport, functional, and storage pools. This incorporation is dose-dependent and follows a kinetic pattern that is characteristic for each pool. At sufficient levels of incorporation, EPA and DHA influence the physical nature of cell membranes and membrane protein-mediated responses, eicosanoid generation, cell signaling and gene expression in many different cell types. Through these mechanisms, EPA and DHA influence cell and tissue physiology, and the way cells and tissues respond to external signals. In most cases, the effects seen are compatible with improvements in disease biomarker profiles or in health-related outcomes. As a result, very long chain omega-3 fatty acids play a role in achieving optimal health and in protection against disease. Long chain omega-3 fatty acids protect against cardiovascular morbidity and mortality, and might be beneficial in rheumatoid arthritis, inflammatory bowel diseases, childhood learning, and behavior, and adult psychiatric and neurodegenerative illnesses. DHA has an important structural role in the eye and brain, and its supply early in life is known to be of vital importance. On the basis of the recognized health improvements brought about by long chain omega-3 fatty acids, recommendations have been made to increase their intake. (C) 2009 International Union of Biochemistry and Molecular Biology, Inc. Volume 35, Number 3, May/June 2009, Pages 266-272. E-mail: pcc@soton.ac.uk

Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [C-13]alpha-linolenic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men

The effect of increased dietary intakes of alpha-linolenic acid (ALNA) or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 2 months upon plasma lipid composition and capacity for conversion of ALNA to longer-chain metabolites was investigated in healthy men (52 (SD 12) years). After a 4-week baseline period when the subjects substituted a control spread, a test meal containing [U-C-13]ALNA (700 mg) was consumed to measure conversion to EPA, docosapentaenoic acid (DPA) and DHA over 48 h. Subjects were then randomised to one of three groups for 8 weeks before repeating the tracer study: (1) continued on same intake (control, n 5); (2) increased ALNA intake (10 g/d, n 4); (3) increased EPA+DHA intake (1.5 g/d, n 5). At baseline, apparent fractional conversion of labelled ALNA was: EPA 2.80, DPA 1.20 and DRA 0.04%. After 8 weeks on the control diet, plasma lipid composition and [C-13]ALNA conversion remained unchanged compared with baseline. The high-ALNA diet resulted in raised plasma triacylglycerol-EPA and -DPA concentrations and phosphatidylcholine-EPA concentration, whilst [C-13]ALNA conversion was similar to baseline. The high-(EPA+DHA) diet raised plasma phosphatidylcholine-EPA and -DHA concentrations, decreased [C-13]ALNA conversion to EPA (2-fold) and DPA (4-fold), whilst [C-13]ALNA conversion to DHA was unchanged. The dietary interventions did not alter partitioning of ALNA towards beta-oxidation. The present results indicate ALNA conversion was down-regulated by increased product (EPA+DHA) availability, but was not up-regulated by increased substrate (ALNA) consumption. This suggests regulation of ALNA conversion may limit the influence of variations in dietary n-3 fatty acid intake on plasma lipid compositions.

Free amino acids and sugars in rye grain: implications for acrylamide formation

Acrylamide forms from free asparagine and sugars during cooking, and products derived from the grain of cereals, including rye, contribute a large proportion of total dietary intake. In this study, free amino acid and sugar concentrations were measured in the grain of a range of rye varieties grown at locations in Hungary, France, Poland, and the United Kingdom and harvested in 2005, 2006, and 2007. Genetic and environmental (location and harvest year) effects on the levels of acrylamide precursors were assessed. The data showed free asparagine concentration to be the main determinant of acrylamide formation in heated rye flour, as it is in wheat. However, in contrast to wheat, sugar, particularly sucrose, concentration also correlated both with asparagine concentration and with acrylamide formed. Free asparagine concentration was shown to be under genetic (G), environmental (E), and integrated (G × E) control. The same was true for glucose, whereas maltose and fructose were affected mainly by environmental factors and sucrose was largely under genetic control. The ratio of variation due to varieties (genotype) to the total variation (a measure of heritability) for free asparagine concentration in the grain was 23%. Free asparagine concentration was closely associated with bran yield, whereas sugar concentration was associated with low Hagberg falling number. Rye grain was found to contain much higher concentrations of free proline than wheat grain, and less acrylamide formed per unit of asparagine in rye than in wheat flour.

Asymmetric synthesis of cyclic β-amino acids and cyclic amines via sequential diastereoselective conjugate addition and ring closing metathesis

Diastereoselective conjugate addition of lithium (S)-N-allyl-N-alpha-methylbenzylamide to a range of alpha,beta-unsaturated esters followed by ring closing metathesis is used to afford efficiently a range of substituted cyclic beta-amino esters in high d.e. Alternatively, conjugate addition to alpha,beta-unsaturated Weinreb amides, functional group conversion and ring closing metathesis affords cyclic amines in high d.e. The further application of this methodology to the synthesis of a range of carbocyclic beta-amino esters via conjugate addition, enolate alkylation and ring closing metathesis is also described. Application of this methodology affords, after deprotection, (S)-homoproline, (S)-homopipecolic acid, (S)-coniine and (1S,2S)-trans-pentacin.

Trans fatty acids and weight gain

Increasing rates of obesity have stimulated research into possible contributing factors, including specific dietary components such as trans fatty acids (TFAs). This review considers the evidence for an association between TFA intake and weight gain. It concludes that there is limited but consistent evidence from epidemiological studies, and from a primate model, that increased TFA consumption may result in a small additional weight gain. Data from a long-term study in a primate model suggest that TFA may have a greater adipogenic effect than cis monounsaturated fatty acids; however, there are currently inadequate mechanistic data to provide a comprehensive and plausible explanation for any such metabolic differences between the types of fatty acids.

Dietary monounsaturated fatty acids and haemostasis

Diets high in monounsaturated fatty acids (MUFA) are increasingly being recommended as a highly-effective cholesterol-lowering strategy in populations at risk of CHD. However, the need for a re-appraisal of the benefits of diets rich in MUFA became apparent as a result of recent studies showing that meals high in olive oil cause greater postprandial activation of blood coagulation factor VII than meals rich in saturated fatty acids. The present review evaluates the evidence for the effects of MUFA-rich diets on fasting and postprandial measurements of haemostasis, and describes data from a recently-completed long-term controlled dietary intervention study. The data show that a background diet high in MUFA has no adverse effect on fasting haemostatic variables and decreases the postprandial activation of factor VII in response to a standard fat-containing meal. Since the same study also showed a significant reduction in the ex vivo activation of platelets in subjects on the high-MUFA diet, the overall findings suggest that there is no reason for concern regarding adverse haemostatic consequences of high-MUFA diets.

Dietary fatty acids and human health

A considerable amount of evidence has accumulated to support the view that the very long chain omega 3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) have beneficial cardiovascular and anti-inflammatory properties and that levels of their consumption are insufficient in most Western diets. More recently, attention has been given to the possibility that the precursor omega-3 PUFA, alpha linolenic acid (ALNA), may share some of the beneficial actions of EPA/DHA on human health. Further research into the metabolism and physiological actions of ALNA, and comparisons with EPA/DHA, is needed before conclusions regarding the optimal amounts and types of omega-3 PUFA for human health can be defined. Conjugated linoleic acid (CLA), which arises as a metabolic by-product of rumen hydrogenation and which is found in foods of animal origin, has been proposed to possess potent health promoting properties, but much of this research has been conducted in experimental animals. There is an urgent need for complementary studies in human volunteers, to confirm the putative anti-carcinogenic, anti-atherogenic, anti-lipogenic and immuno-suppressive properties of CLA.

Synthesis and incorporation into cyclic peptides of tolan amino acids and their hydrogenated congeners: construction of an array of A–B-loop mimetics of the Cε3 domain of human IgE

The disruption of the human immunolobulin E–high affinity receptor I (IgE–FcεRI) protein–protein interaction (PPI) is a validated strategy for the development of anti asthma therapeutics. Here, we describe the synthesis of an array of conformationally constrained cyclic peptides based on an epitope of the A–B loop within the Cε3 domain of IgE. The peptides contain various tolan (i.e., 1,2-biarylethyne) amino acids and their fully and partially hydrogenated congeners as conformational constraints. Modest antagonist activity (IC50 660 μM) is displayed by the peptide containing a 2,2′-tolan, which is the one predicted by molecular modeling to best mimic the conformation of the native A–B loop epitope in IgE.