Dietary interventions affecting chylomicron and chylomicron remnant clearance

Interest in effects of diet on postprandial lipoproteins has increased in recent years as a result of accumulating evidence for adverse cardiovascular consequences of elevated concentrations of triglyceride rich lipoproteins. Particular attention has been given to ability of different fatty acids to modulate postprandial lipoprotein responses because of evidence for both harmful and protective cardiovascular properties of the saturated, monounsaturated and ω-6 and ω-3 polyunsaturated fatty acid (PUFA) classes. Evidence for direct atherogenic properties of chylomicron remnants has led to attempts to monitor effects of diet specifically on this lipoprotein class. Limitations in the methods employed to measure chylomicron remnants and the small number of human studies which have evaluated effects of meal, and background diet, fatty acid composition, makes it difficult to draw definitive conclusions at the present time. However consideration of data from both animal and human studies tends to support the conclusion that diets, and meals, rich in PUFA (particularly long chain ω-3 PUFA), result in attenuated postprandial responses of the intestinally-derived lipoproteins. Attenuated responses to high PUFA meals appear to be due to greater rates of clearance and greater activation of lipoprotein lipase (LPL). Attenuated responses to high PUFA background diets may be due to adaptive changes involving both accelerated rates of clearance in peripheral tissues and liver, as well as decreased output of the competitor for chylomicron clearance, very low density lipoprotein (VLDL).

Variation in the FFAR1 gene modifies BMI, body composition and plasma lipids but not plasma insulin or Beta-cell function in overweight subjects

Background FFAR1 receptor is a long chain fatty acid G-protein coupled receptor which is expressed widely, but found in high density in the pancreas and central nervous system. It has been suggested that FFAR1 may play a role in insulin sensitivity, lipotoxicity and is associated with type 2 diabetes. Here we investigate the effect of three common SNPs of FFAR1 (rs2301151; rs16970264; rs1573611) on pancreatic function, BMI, body composition and plasma lipids. Methodology/Principal Findings For this enquiry we used the baseline RISCK data, which provides a cohort of overweight subjects at increased cardiometabolic risk with detailed phenotyping. The key findings were SNPs of the FFAR1 gene region were associated with differences in body composition and lipids, and the effects of the 3 SNPs combined were cumulative on BMI, body composition and total cholesterol. The effects on BMI and body fat were predominantly mediated by rs1573611 (1.06 kg/m2 higher (P = 0.009) BMI and 1.53% higher (P = 0.002) body fat per C allele). Differences in plasma lipids were also associated with the BMI-increasing allele of rs2301151 including higher total cholesterol (0.2 mmol/L per G allele, P = 0.01) and with the variant A allele of rs16970264 associated with lower total (0.3 mmol/L, P = 0.02) and LDL (0.2 mmol/L, P<0.05) cholesterol, but also with lower HDL-cholesterol (0.09 mmol/L, P<0.05) although the difference was not apparent when controlling for multiple testing. There were no statistically significant effects of the three SNPs on insulin sensitivity or beta cell function. However accumulated risk allele showed a lower beta cell function on increasing plasma fatty acids with a carbon chain greater than six. Conclusions/Significance Differences in body composition and lipids associated with common SNPs in the FFAR1 gene were apparently not mediated by changes in insulin sensitivity or beta-cell function.

DHA-rich fish oil reverses the detrimental effects of saturated fatty acids on postprandial vascular reactivity

Background: Experimental elevation of nonesterified fatty acids (NEFAs) impairs endothelial function, but the effect of NEFA composition is unknown. Objective: The objective was to test the effect of acute elevation of NEFAs enriched with either saturated fatty acids (SFAs) or SFAs with long-chain (LC) n−3 (omega-3) PUFAs on vascular function measured via flow-mediated dilatation (FMD), laser Doppler iontophoresis (LDI), and digital volume pulse (DVP). Design: In 59 subjects (30 men and 29 women), repeated oral fat feeding of either palm stearin (SFA) or palm stearin with DHA-rich fish oil (SFA + LC n−3 PUFA) was performed on 2 separate occasions with continuous heparin infusion to elevate NEFAs for a duration of 60 to 240 min. Vascular function was measured at baseline and at the end of NEFA elevation; venous blood was collected for measurement of lipids and circulating markers of endothelial function. Results: NEFA elevation during consumption of the SFA-rich drinks was associated with a marked impairment of FMD, whereas consumption of SFAs + LC n−3 PUFAs improved FMD response, with a mean (±SEM) difference of 2.06 ± 0.29% (P < 0.001). Positive correlations were found with percentage weight of LC n−3 PUFAs in circulating NEFAs and change in FMD response [Spearman's rho (rs) = 0.460, P < 0.001]. LDI measures increased during both treatments (P ≤ 0.026), and there was no change in DVP indexes. Conclusions: The composition of NEFAs can acutely affect FMD. The beneficial effect of LC n−3 PUFAs on postprandial vascular function warrants further investigation but may be mediated by nitric oxide–independent mechanisms. This trial is registered at clinicaltrials.gov as NCT01351324.

Effects of omega-3 fatty acids on immune function in broiler chickens

There is interest in the enrichment of poultry meat with long-chain n-3 polyunsaturated fatty acids in order to increase the consumption of these fatty acids by humans. However, there is concern that high levels of n-3 polyunsaturated fatty acids may have detrimental effects on immune function in chickens. The effect of feeding increasing levels of fish oil (FO) on immune function was investigated in broiler chickens. Three-week-old broilers were fed 1 of 4 wheat-soybean basal diets that contained 0, 30, 50, or 60 g/kg of FO until slaughter. At slaughter, samples of blood, bursa of Fabricius, spleen, and thymus were collected from each bird. A range of immune parameters, including immune tissue weight, immuno-phenotyping, phagocytosis, and cell proliferation, were assessed. The pattern of fatty acid incorporation reflected the fatty acid composition of the diet. The FO did not affect the weight of the spleen, but it did increase thymus weight when fed at 50 g/kg (P < 0.001). Fish oil also lowered bursal weights when fed at 50 or 60 g/kg (P < 0.001). There was no significant effect of FO on immune cell phenotypes in the spleen, thymus, bursa, or blood. Feeding 60 g/kg of FO significantly decreased the percentage of monocytes engaged in phagocytosis, but it increased their mean fluorescence intensity relative to that of broilers fed 50 g/kg of FO. Lymphocyte proliferation was significantly decreased after feeding broiler chickens diets rich in FO when expressed as division index or proliferation index, although there was no significant effect of FO on the percentage of divided cells. In conclusion, dietary n-3 polyunsaturated fatty acids decrease phagocytosis and lymphocyte proliferation in broiler chickens, highlighting the need for the poultry industry to consider the health status of poultry when poultry meat is being enriched with FO.

Application of the BRAFO-tiered approach for benefit-risk assessment to case studies on natural foods

There is evidence that consumption of fish, especially oily fish, has substantial beneficial effects on health. In particular an inverse relationship of oily fish intake to coronary heart disease incidence has been established. These beneficial effects are ascribed to fish oil components including long chain ω-3 polyunsaturated fatty acids. On the other hand it should be noted that oily fish also contains hazardous substances such as dioxins, PCBs and methylmercury. Soy consumption has been associated with potential beneficial and adverse effects. The claimed benefits include reduced risk of cardiovascular disease; osteoporosis, breast and prostate cancer whereas potential adverse effects include impaired thyroid function, disruption of sex hormone levels, changes in reproductive function and increased breast cancer risk The two cases of natural foods highlight the need to consider both risks and benefits in order to establish the net health impact associated to the consumption of specific food products. Within the Sixth Framework programme of the European Commission, the BRAFO project was funded to develop a framework that allows for the quantitative comparison of human health risks and benefits in relation to foods and food compounds. This paper describes the application of the developed framework to two natural foods, farmed salmon and soy protein. We conclude that the BRAFO methodology is highly applicable to natural foods. It will help the benefit-risk managers in selecting the appropriate dietary recommendations for the population.

Obesity and body fat classification in the metabolic syndrome: impact on cardiometabolic risk metabotype

Obesity is a key factor in the development of the metabolic syndrome (MetS), which is associated with increased cardiometabolic risk. We investigated whether obesity classification by body mass index (BMI) and body fat percentage (BF%) influences cardiometabolic profile and dietary responsiveness in 486 MetS subjects (LIPGENE dietary intervention study). Anthropometric measures, markers of inflammation and glucose metabolism, lipid profiles, adhesion molecules and haemostatic factors were determined at baseline and after 12 weeks of 4 dietary interventions (high saturated fat (SFA), high monounsaturated fat (MUFA) and 2 low fat high complex carbohydrate (LFHCC) diets, 1 supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs)). 39% and 87% of subjects classified as normal and overweight by BMI were obese according to their BF%. Individuals classified as obese by BMI (± 30 kg/m2) and BF% (± 25% (men) and ± 35% (women)) (OO, n = 284) had larger waist and hip measurements, higher BMI and were heavier (P < 0.001) than those classified as non-obese by BMI but obese by BF% (NOO, n = 92). OO individuals displayed a more pro-inflammatory (higher C reactive protein (CRP) and leptin), pro-thrombotic (higher plasminogen activator inhibitor-1 (PAI-1)), pro-atherogenic (higher leptin/adiponectin ratio) and more insulin resistant (higher HOMA-IR) metabolic profile relative to the NOO group (P < 0.001). Interestingly, tumour necrosis factor alpha (TNF-α) concentrations were lower post-intervention in NOO individuals compared to OO subjects (P < 0.001). In conclusion, assessing BF% and BMI as part of a metabotype may help identify individuals at greater cardiometabolic risk than BMI alone.

Salmon consumption during pregnancy alters fatty acid composition and secretory IgA concentration in human breast milk

Fish oil supplementation during pregnancy alters breast milk composition, but there is little information about the impact of oily fish consumption. We determined whether increased salmon consumption during pregnancy alters breast milk fatty acid composition and immune factors. Women (n = 123) who rarely ate oily fish were randomly assigned to consume their habitual diet or to consume 2 portions of farmed salmon per week from 20 wk of pregnancy until delivery. The salmon provided 3.45 g long-chain (LC) (n-3) PUFA/wk. Breast milk fatty acid composition and immune factors [soluble CD14, transforming growth factor-b (TGFb)1, TGFb2, and secretory IgA] were analyzed at 1, 5, 14, and 28 d postpartum (PP). Breast milk from the salmon group had higher proportions of EPA (80%), docosapentaenoic acid (30%), and DHA (90%) on d 5 PP compared with controls (P < 0.01). The LC (n-6) PUFA:LC (n-3) PUFA ratio was lower for the salmon group on all days of PP sampling (P < 0.004), although individual (n-6) PUFA proportions, including arachidonic acid, did not differ. All breast milk immune factors decreased between d 1 and 28 PP (P < 0.001). Breast milk secretory IgA (sIgA) was lower in the salmon group (d 1–28 PP; P = 0.006). Salmon consumption during pregnancy, at the current recommended intakes, increases the LC (n-3) PUFA concentration of breast milk in early lactation, thus improving the supply of these important fatty acids to the breast-fed neonate. The consequence of the lower breast milk concentration of sIgA in the salmon group is not clear.

Glu298Asp polymorphism influences the beneficial effects of fish oil fatty acids on postprandial vascular function

Our objective was to determine whether the endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism influences vascular response to raised NEFA enriched with saturated fatty acids (SFA) or long-chain (LC) n-3 polyunsaturated fatty acids (PUFA). Subjects were prospectively recruited for genotype (Glu298, n = 30 and Asp298, n = 29; balanced for age and gender) consumed SFA on two occasions, with and without the substitution of 0.07 g fat/kg body weight with LC n-3 PUFA, and with heparin infusion to elevate NEFA. Endothelial function was measured before and after NEFA elevation (240 min), with blood samples taken every 30 min. Flow-mediated dilation (FMD) decreased following SFA alone and increased following SFA+LC n-3 PUFA. There were 2-fold differences in the change in FMD response to the different fat loads between the Asp298 and Glu298 genotypes (P = 0.002) and between genders (P < 0.02). Sodium nitroprusside-induced reactivity, measured by laser Doppler imaging with iontophoresis, was significantly greater with SFA+LC n-3 PUFA in all female subjects (P < 0.001) but not in males. Elevated NEFA influences both endothelial-dependent and endothelial-independent vasodilation during the postprandial phase. Effects of fat composition appear to be genotype and gender dependent, with the greatest difference in vasodilatory response to the two fat loads seen in the Asp298 females.

An investigation into the pathogenic properties of Escherichia coli strains BLR, BL21, DH5 alpha and EQ1

Aims: To examine Escherichia coli strains EQ1, DH5 alpha, BLR and BL21 for known pathogenic mechanisms. Methods and Results: Using specific DNA probes, the strains were shown not to carry the genes encoding invasion, various adhesion phenotypes or expression of a range of enterotoxins. The strains were unable to express long-chain lipopolysaccharide and were susceptible to the effects of serum complement. Using a BALB/c mouse model, the strains were shown to be unable to survive in selected tissues or to persist in the mouse gut. Using a chick model, strains EQ1, BLR and BL21 invaded livers but not spleens; only strain EQ1 persisted in the chick gut. In Merino sheep, only strain EQ1 was detected 6 d postinfection. Conclusions: Escherichia coli strains EQ1, DH5 alpha, BLR and BL21 did not carry the well-recognized pathogenic mechanisms required by strains of E. coli causing the majority of enteric infections. Significance and Impact of the Study: Escherichia coli strains EQ1, DH5 alpha, BLR and BL21 were considered to be non-pathogenic and unlikely to survive in host tissues and cause disease.

Fatty acid composition of cooked chicken meat and chicken meat products as influenced by price range at retail

The primary objective was to determine fatty acid composition of skinless chicken breast and leg meat portions and chicken burgers and nuggets from the economy price range, standard price range (both conventional intensive rearing) and the organic range from four leading supermarkets. Few significant differences in the SFA, MUFA and PUFA composition of breast and leg meat portions were found among price ranges, and supermarket had no effect. No significant differences in fatty acid concentrations of economy and standard chicken burgers were found, whereas economy chicken nuggets had higher C16:1, C18:1 cis, C18:1 trans and C18:3 n-3 concentrations than had standard ones. Overall, processed chicken products had much higher fat contents and SFA than had whole meat. Long chain n-3 fatty acids had considerably lower concentrations in processed products than in whole meat. Overall there was no evidence that organic chicken breast or leg meat had a more favourable fatty acid composition than had meat from conventionally reared birds.

SANS/WANS time-resolving neutron scattering studies of polymer phase transitions using NIMROD

We use new neutron scattering instrumentation to follow in a single quantitative time-resolving experiment, the three key scales of structural development which accompany the crystallisation of synthetic polymers. These length scales span 3 orders of magnitude of the scattering vector. The study of polymer crystallisation dates back to the pioneering experiments of Keller and others who discovered the chain-folded nature of the thin lamellae crystals which are normally found in synthetic polymers. The inherent connectivity of polymers makes their crystallisation a multiscale transformation. Much understanding has developed over the intervening fifty years but the process has remained something of a mystery. There are three key length scales. The chain folded lamellar thickness is ~ 10nm, the crystal unit cell is ~ 1nm and the detail of the chain conformation is ~ 0.1nm. In previous work these length scales have been addressed using different instrumention or were coupled using compromised geometries. More recently researchers have attempted to exploit coupled time-resolved small-angle and wide-angle x-ray experiments. These turned out to be challenging experiments much related to the challenge of placing the scattering intensity on an absolute scale. However, they did stimulate the possibility of new phenomena in the very early stages of crystallisation. Although there is now considerable doubt on such experiments, they drew attention to the basic question as to the process of crystallisation in long chain molecules. We have used NIMROD on the second target station at ISIS to follow all three length scales in a time-resolving manner for poly(e-caprolactone). The technique can provide a single set of data from 0.01 to 100Å-1 on the same vertical scale. We present the results using a multiple scale model of the crystallisation process in polymers to analyse the results.

Fish oil fatty acids and vascular reactivity

Endothelial dysfunction and an associated increase in vascular tone are risk factors for cardiovascular disease and highly predictive of future cardiovascular events. A part of the benefits associated with increased intake of the long chain (LC) n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid and docosahexaenoic acid, found in fish oils is a positive impact on cardiovascular health. Here, the recent evidence from human observational and intervention trials are reviewed, and an insight into potential mechanisms underlying the impact of LC n-3 PUFA on vascular reactivity is provided.

Dairy fat: perceptions and realities.

Milk provides many key nutrients but the saturated and trans fatty acids in milk fat are associated with perceived negative effects on human health, especially cardiovascular disease. Recent epidemiological studies and dietary intervention trials challenge this perception, however; available evidence does not support the concept that consumption of saturated fats or dairy products adversely affects the risk of coronary heart disease (although replacing some saturated fats with mono or polyunsaturated fats is likely to provide benefit). Furthermore, the trans fats found in dairy products are consumed in very low amounts and do not appear to have the negative health effects associated with the consumption of industrial sources of trans fat. Milk fat is an excellent source of oleic acid that originates mainly by endogenous synthesis from stearic acid, but increasing the milk fat content of unsaturated fatty acids requires dietary formulations that bypass rumen biohydrogenation. Recent research indicates that long-chain omega-3 fatty acids and conjugated linoleic acids have potential beneficial effects in health maintenance and the prevention of chronic diseases. Enhancing the milk fat content of these fatty acids offers exciting possibilities, but educating consumers about inaccurate and inappropriate generalisations about fat remains the primary challenge. Finally, individuals do not simply consume milk-fat-derived fatty acids on their own, but rather as components in dairy foods which are highly complex and may contain many beneficial ingredients. Overall, dairy products are critical in providing many of the essential nutrients in the human diet. Nevertheless, dairy products vary in their nutrient composition, including fat, and this needs to be considered in the context of dietary recommendations and our need to consume a balanced diet.

Investigations into the formation and characterization of phospholipid microemulsions. IV. Pseudo-ternary phase diagrams of systems containing water-lecithin-alcohol and oil; The influence of oil

Phase studies have been performed for quaternary systems composed of egg lecithin, cosurfactant, water and oil. The lecithin used was the commercially available egg lecithin Ovothin 200 (which comprises ≥ 92% phosphatidylcholine). The cosurfactants employed were propanol and butanol, and these were used at lecithin/cosurfactant mixing ratios (Km) of 1:1 and 1.94:1 (weight basis). Six polar oils were investigated, including the alkanoic acids, octanoic and oleic, their corresponding ethyl esters and the medium and long chain triglycerides, Miglyol 812 and soybean oil. All oils, irrespective of the alcohol and the Km used, gave rise to systems that produced a stable isotropic region along the surfactant/oil axis (designated as a reverse microemulsion system). In addition, the systems incorporating propanol at both Km and butanol at a Km of 1.94: 1, generally gave rise to a liquid crystalline region and, in some cases, a second isotropic non-birefingent area (designated as a normal microemulsion system). The phase behaviour observed was largely dependent upon the alcohol and Km used and the size and the polarity of the oil present.

Fish oil supplementation alters numbers of circulating endothelial progenitor cells and micro particles independent of eNOS genotype

Background Emerging cellular markers of endothelial damage and repair include endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) respectively. Effects of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) and influence of genetic background on these markers are not known. Objective This study investigated the effects of fish oil supplementation on both classical and novel markers of endothelial function in subjects prospectively genotyped for the Asp298 eNOS polymorphism and at moderate risk of CVD. Design 84 subjects with moderate risk of CVD (n=40 GG and n=44 GT/TT) completed a randomized, double-blind, placebo-controlled, 8-week cross-over trial of fish oil supplementation providing 1.5 g/d LC n-3 PUFA. Effects of genotype and fish oil supplementation on the blood lipid profile, inflammatory markers, vascular function (EndoPAT) and numbers of circulating EPCs and EMP (flow cytometry) were assessed. Results There was no significant effect of fish oil supplementation on blood pressure, plasma lipids or plasma glucose, although there was a trend (P = 0.069) towards a decrease in plasma TG concentration after FO supplementation compared to placebo. GT/TT subjects tended to have higher levels of total cholesterol and LDL-cholesterol, but vascular function was not affected by either treatment or eNOS genotype. Biochemical markers of endothelial function were also unaffected by treatment and eNOS genotype. In contrast, there was a significant effect of fish oil supplementation on cellular markers of endothelial function. Fish oil supplementation increased numbers of EPCs and reduced numbers of EMPs relative to the placebo, potentially favouring maintenance of endothelial integrity. There was no influence of genotype for any of the cellular markers of endothelial function, indicating that the effects of fish oil supplementation were independent of eNOS genotype. Conclusions Emerging cellular markers of endothelial damage, integrity and repair appear to be sensitive to potentially beneficial modification by dietary n-3 PUFA.