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Background & aims: Legumes, a low-energy, nutrient-dense and low glycemic index food, have shown beneficial effects on glycemic control and adiposity. As such, legumes are widely recommended in diabetic diets, even though there is little evidence that their consumption protects against type 2 diabetes. Therefore the aim of the present study was to examine the associations between consumption of total legumes and specific subtypes, and type 2 diabetes risk. We also investigated the effect of theoretically substituting legumes for other protein- or carbohydrate-rich foods. Methods: Prospective assessment of 3349 participants in the PREvención con DIeta MEDiterránea (PREDIMED) study without type 2 diabetes at baseline. Dietary information was assessed at baseline and yearly during follow-up. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for type-2 diabetes incidence according to quartiles of cumulative average consumption of total legumes, lentils, chickpeas, dry beans and fresh peas. Results: During a median follow-up of 4.3 years, 266 new cases of type 2 diabetes occurred. Individuals in the highest quartile of total legume and lentil consumption had a lower risk of diabetes than those in the lowest quartile (HR: 0.65; 95% CI: 0.43, 0.96; P-trend = 0.04; and HR: 0.67; 95% CI: 0.46–0.98; P-trend = 0.05, respectively). A borderline significant association was also observed for chickpeas consumption (HR 0.68; 95% CI: 0.46, 1.00; P-trend = 0.06). Substitutions of half a serving/day of legumes for similar servings of eggs, bread, rice or baked potato was associated with lower risk of diabetes incidence. Conclusions: A frequent consumption of legumes, particularly lentils, in the context of a Mediterranean diet, may provide benefits on type 2 diabetes prevention in older adults at high cardiovascular risk. Trial registration: The trial is registered at http://www.controlled-trials.com (ISRCTN35739639). Registration date: 5th October 2005., The authors disclose no conflict of interest related with the article. Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN) is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds (CB06/03). Supported by the official funding agency for biomedical research of the Spanish government, ISCIII, through grants provided to research networks specifically developed for the trial (RTIC G03/140 and RD 06/0045) through CIBEROBN, and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigación Sanitaria–FondoEuropeo de Desarrollo Regional (PI04–2239, PI05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, and PI11/02505; PI13/00462), Ministerio de Ciencia e Innovación (AGL-2009–13906-C02 and AGL2010–22319-C03), Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (PI0105/2007), Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (ACOMP06109, GVA-COMP2010–181, GVACOMP2011–151, CS2010-AP-111, and CS2011-AP-042), and the Navarra Regional Government (27/2011). The Fundación Patrimonio Comunal Olivarero and Hojiblanca SA (Málaga, Spain), California Walnut Commission (Sacramento, CA), Borges SA (Reus, Spain), and Morella Nuts SA (Reus, Spain) donated the olive oil, walnuts, almonds, and hazelnuts, respectively, used in the study. None of the funding sources played a role in the design, collection, analysis or interpretation of the data or in the decision to submit the manuscript for publication. Acknowledgements: The authors thank all the participants for their collaboration, all the PREDIMED personnel for their assistance and all the personnel of affiliated primary care centers for making the study possible. CIBEROBN is an initiative of ISCIII, Spain.

© 2014 Elsevier B.V. Background and aim: Hypertension is one of the main cardiovascular risk factors in the elderly. The aims of this work were to evaluate if a one-year intervention with two Mediterranean diets (Med-diet) could decrease blood pressure (BP) due to a high polyphenol consumption, and if the decrease in BP was mediated by plasma nitric oxide (NO) production. Methods and results: An intervention substudy of 200 participants at high cardiovascular risk was carried out within the PREDIMED trial. They were randomly assigned to a low-fat control diet or to two Med-diets, one supplemented with extra virgin olive oil (Med-EVOO) and the other with nuts (Med-nuts). Anthropometrics and clinical parameters were measured at baseline and after one year of intervention, as well as BP, plasma NO and total polyphenol excretion (TPE) in urine samples. Systolic and diastolic BP decreased significantly after a one-year dietary intervention with Med-EVOO and Med-nuts. These changes were associated with a significant increase in TPE and plasma NO. Additionally, a significant positive correlation was observed between changes in urinary TPE, a biomarker of TP intake, and in plasma NO (Beta=4.84; 95% CI: 0.57-9.10). Conclusions: TPE in spot urine sample was positively correlated with plasma NO in Med-diets supplemented with either EVOO or nuts. The statistically significant increases in plasma NO were associated with a reduction in systolic and diastolic BP levels, adding to the growing evidence that polyphenols might protect the cardiovascular system by improving the endothelial function and enhancing endothelial synthesis of NO., We would like to thank all the volunteers involved in the PREDIMED study for their valuable cooperation. This study was supported in part by CICYT (AGL2010-22319-C03 and AGL2013-49083-C3-1-R), RD06/0045 and CIBEROBN from the ISCIII (Spanish Ministry of Science and Innovation, MICINN), Quality Group from Generalitat de Catalunya 2009-SGR-724 and 2014-SGR-773, and Grant of support to research groups no.35/2011 (Balearic Islands Gov. and EU FEDER funds). A.M.-R. thanks the “Juan de la Cierva” postdoctoral program (JCI-2012-13463) from MEC. A.T.-R. would like to thank the ISCIII for granting her a predoctoral fellowship (FI10/00265).

[Objective]: The PREDIMED trial showed that Mediterranean diets supplemented with either extra-virgin olive oil or nuts reduced incident cardiovascular events compared to a control diet. Consumption of both supplemental foods has been associated with reduced LDL-cholesterol, but it is unknown whether they can shift lipoprotein subfractions to a less atherogenic pattern. We investigated changes in adiposity and lipoprotein subfractions after consumption of the PREDIMED diets., [Methods]: In a PREDIMED sub-cohort (n = 169), lipoprotein subclasses (particle concentrations and size) were determined by nuclear magnetic resonance spectroscopy at baseline and after intervention for 1 year., [Results]: Participants allocated to the Mediterranean diet supplemented with nuts showed significant reductions from baseline of waist circumference (mean [95% CI]; −5 cm [−7; −3]) and concentrations of medium-small (−27 nmol/l [−46; −8]) and very small LDL (−111 nmol/l [−180; −42]); decreased LDL particle number (a nuclear magnetic resonance-specific measurement) (−98 nmol/l [−184; −11]); and an increase of large LDL concentrations (54 nmol/l [18; 90]), with a net increase (0.2 nmol/l [0.1; 0.4]) of LDL size. The Mediterranean diets with olive oil and nuts increased large HDL concentrations (0.6 μM [0.0; 1.1] and 1.0 μM [0.4; 1.5], respectively). Compared to the other two intervention groups, participants in the nut-enriched diet showed significantly reduced waist circumference (p ≤ 0.006, both) and increased LDL size (p < 0.05, both)., [Conclusion]: Lipoprotein subfractions are shifted to a less atherogenic pattern by consumption of Mediterranean diets enriched with nuts. The results contribute mechanistic evidence for the reduction of cardiovascular events observed in the PREDIMED trial., This study was funded in part by ISCIII (Spanish Ministry of Economy) through grants RTIC G03/140, RTIC RD 06/0045, and FIS PS09/01292 and grant CNIC 06/2007 from Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. AS-V was supported by post-doctoral contract FIS CD07/0083. MF was supported by a joint contract of ISCIII and the Health Department of the Catalan Government (Generalitat de Catalunya), CP 06/00100.

Objective Observational studies have reported inverse associations between adherence to the Mediterranean diet (MedDiet) and atherosclerotic disease. We tested the effect of two types of MedDiet on progression of subclinical carotid atherosclerosis. Methods We randomized 187 high-cardiovascular-risk asymptomatic subjects (51% women, mean age 67 years) to three treatment arms: MedDiet with supplemental virgin olive oil (VOO), n = 66; MedDiet with supplemental nuts, n = 59; and control diet, n = 62. Participants received nutrition behavioral counseling in quarterly group and individual educational sessions. Free supplemental foods were provided to the MedDiet groups. Changes in mean intima-media thickness (IMT) were measured ultrasonographically in the far wall of bilateral common carotid arteries after 1 year. Results Overall, no significant between-group differences in IMT progression were observed after 1-year. However, a significant interaction (p = 0.03) between baseline IMT and treatment effect was apparent. Among participants with baseline IMT ≥ 0.9 mm, 1-year IMT changes versus control showed significant differences of −0.079 mm (95% confidence interval, −0.145 to −0.012) for the MedDiet with VOO and −0.072 mm (−0.140 to −0.004) for the MedDiet with nuts. No IMT changes occurred in any intervention group among participants with lower baseline IMT values (, Spanish Government (FIS-ISCIII, PI050976, PI070240, PI081943, PI1002293, RTIC 06/0045, CIBERobn, and CNIC/06); Government of Navarra (PI41/2005, PI36/2008). RTIC 06/0045 and CIBERobn are initiatives of ISCIII, Spanish Government.

Free triterpenic acids (TTPs) present in plants are bioactive compounds exhibiting multiple nutriceutical activities. The underlying molecular mechanisms have only been examined in part and mainly focused on anti-inflammatory properties, cancer and cardiovascular diseases, in all of which TTPs frequently affect membrane-related proteins. Based on the structural characteristics of TTPs, we assume that their effect on biophysical properties of cell membranes could play a role for their biological activity. In this context, our study is focused on the compounds, oleanolic (3β-hydroxy-12- oleanen-28-oic acid, OLA), maslinic (2α,3β-dihydroxy-12-oleanen-28- oic acid, MSL) and ursolic ((3β)-3-hydroxyurs-12-en-28-oic acid, URL) as the most important TTPs present in orujo olive oil. X-ray diffraction, differential scanning calorimetry, 31P nuclear magnetic resonance and Laurdan fluorescence data provide experimental evidence that OLA, MSL and URL altered the structural properties of 1,2-dipalmitoyl-sn-glycero-3- phosphatidylcholine (DPPC) and DPPC-Cholesterol (Cho) rich membranes, being located into the polar-hydrophobic interphase. Specifically, in DPPC membranes, TTPs altered the structural order of the Lβ′, phase without destabilizing the lipid bilayer. The existence of a nonbilayer isotropic phase in coexistence with the liquid crystalline Lα phase, as observed in DPPC:URL samples, indicated the presence of lipid structures with high curvature (probably inverted micelles). In DPPC:Cho membranes, TTPs affected the membrane phase properties increasing the Laurdan GP values above 40 °C. MSL and URL induced segregation of Cho within the bilayer, in contrast to OLA, that reduced the structural organization of the membrane. These results strengthen the relevance of TTP interactions with cell membranes as a molecular mechanism underlying their broad spectrum of biological effects. © 2010 Elsevier B.V. All rights reserved., This research has received funding from the European Community's Seventh Framework Programme (FP7/2007–2013): DESY-HASYLAB-Project No. II-20090005 EC, “Comision Interministerial de Ciencia y Tecnología” (CICYT, AGL2008-02258) and “Instituto de Salud Carlos III” (RD06/0045).

1 página. Proceedings and Abstracts of the 2nd International Symposium on Chylomicrons in Disease-2 (ISCD2), Resúmen póster.

Publisher Summary The Mediterranean diet is associated with a reduced risk of cardiovascular mortality despite the high intake of fat, mainly derived from olive oil. Olive oil is a fruit juice with a complex composition where triglycerides of oleic acid are the main component but other biologically active compounds such as tocopherols, phenols, phytosterols, and triterpenoids are also present. This chapter proposes that these components might be responsible for the benefits of virgin olive oil in animal models and in human studies. Hydroxytyrosol, as a simple phenol or conjugate form, is present in a particularly high concentration in extra virgin olive oil, representing around 10% of the total phenolic content (5–80 mg kg –1 ). Several studies have demonstrated that hydroxytyrosol is absorbed and excreted in urine as a response to the intake of virgin olive oil as well as to the intake of oily and aqueous preparations. Hydroxytyrosol has been recovered in all lipoprotein fractions, except in very low-density lipoproteins (VLDL), after extra virgin olive oil ingestion. Studies have been carried out on hydroxytyrosol in the in vivo atherosclerosis process using the apoE-deficient mouse as a model of spontaneous atherosclerosis development. These animals develop severe atherosclerosis on a regular low-fat/low-cholesterol diet. The progression and histopathology of lesions in this animal model show similar features to those observed in humans and other species.

Publisher Summary The postprandial lipid period takes place after the intake of food. Therefore, postprandial lipid metabolism refers to the metabolic processes that occur following the ingestion of a meal containing fat, and it is characterized by a considerable increase in plasma triglyceride (TG) levels. The postprandial response can last up to 8 hours depending on the amount and type of ingested fat. Thus, due to the frequency of intake in developed countries, most humans are in an almost constant postprandial state. Together with elevated plasma TG, an impaired metabolism of postprandial triglyceride-rich lipoproteins (TRL) is believed to contribute to the onset and development of atherosclerosis. TRL comprise a very heterogeneous group of nascent and metabolically modified lipoproteins, including chylomicrons (CM), very-low-density lipoproteins (VLDL), and their remnants. CM are assembled in the intestine and mainly contain dietary lipids, while VLDL include lipids from endogenous origin. TRL become remnant particles after partial depletion of their TG content by lipoprotein lipase (LPL) hydrolysis. These types of particles are highly atherogenic because, in contrast to low-density lipoproteins, TRL can penetrate into the intima and be taken up by macrophages without need for prior oxidation, leading to foam cell formation, which is one of the first steps in atherosclerosis development. In addition, each TRL transports more cholesterol than does each particle of low-density lipoproteins (LDL), delivering to the intima 5- to 20-fold more cholesterol and therefore, being potentially more atherogenic than LDL. The atherogenicity of TRL is influenced by their composition and size, increasing the risk with the augmentation of circulating particles and the time elapsed before their clearance. One of the proposed reasons why dietary fats play a key role in atherogenesis is because dietary lipids contained in CM can interact directly with cells in the artery wall during their plasmatic transport.

Publisher Summary In order to study the normotensive effect of virgin olive oil (VOO) in the elderly, and the possible influence of non-oleic acid components of the oil, two different VOO of the same variety, season and geographic localization were employed. The oils presented a similar composition in minor components and very little differences in oleic and linoleic acids, resulting in significant differences in triacylglycerol (TG) molecular species composition. These oils were administered within the diet to 81 normotensive and hypertensive very old subjects (mean age 84 years) at a home for the elderly for 4 weeks each, including a 4-week washout period with sunflower oil before and in between the VOO. The results corroborated previous studies, demonstrating that VOO consumption can reduce systolic blood pressure in hypertensive subjects. However, it was interesting to note that the concentrations of total and LDL-cholesterol were reduced only after consumption of the VOO with the highest triolein content. The cholesterol reduction was related with the TG molecular species composition of very-low-density lipoproteins (VLDL). In these particles, fatty acids were selectively distributed to form TG after the consumption of either VOO. Since low-density lipoproteins (LDL) are synthesised in plasma from VLDL remnants, LDL formation and composition are, in part, determined by the TG composition of VLDL and the activity of lipoprotein lipase, the enzyme responsible for their hydrolysis. Therefore, it is concluded that the differences in TG molecular species in VOO, and not oleic acid itself, were responsible for the effects on the concentration of plasma cholesterol observed. In contrast, as both VOO studied reduced systolic and diastolic blood pressure, the effect could not be ascribed to TG. Previous studies had suggested that non-oleic acid components can also cause the normotensive effect of VOO. Therefore, these results pointed towards a key role of minor components in this regard.

Publisher Summary Olea europaea L. is a rich source of a variety of pentacyclic triterpenoids including oleanolic acid, maslinic acid, erythrodiol and uvaol, which have shown numerous biological effects. They are the most abundant triterpenoids in the unsaponifiable fraction of virgin olive oil. A special source of these triterpenic compounds is pomace olive oil, called “orujo” olive oil in Spain, which is obtained from the waste of olives (which comprises a blend of olive leaves, cuticle and surface) resulting from the mechanical extraction of virgin olive oil. This olive sub-product contains higher concentrations of triterpenic acids and alcohols than virgin olive oil, exceeding values of 120 mg kg–+. In fact, the total amount of the triterpenic alcohols, erythrodiol plus uvaol, is a parameter of purity to detect the presence of pomace olive oil. Oleanolic acid has been identified as the aglycone of numerous triterpenoid saponins in medicinal plants, as an active component in these plants, contributing to the production of several biological and pharmacological effects. There is a growing interest regarding the biopharmaceutical potential of triterpenoids extracted from pomace olive oil and many studies are currently trying to elucidate the mechanisms underlying their biological and pharmacological activities. This chapter focuses on the main functional properties of natural triterpenoids contained in pomace olive oil and the molecular transduction pathways reported to be involved in these activities.

11 páginas, 8 figuras., Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease for which there exist no therapies without undesired side effects. Thus, the establishment of less toxic treatments is an ongoing challenge. Nowadays, research on medicinal plants has been attracting much attention, since screening of its active principles could prove useful in identification of safe and innovative pharmaceutical molecules. In this study we investigated the therapeutic effect of oleanolic acid (OA) a plant-derived triterpene with potent anti-inflammatory and immunomodulatory activities, whose actions on CNS diseases remain far from completely characterized. We focussed on the potential therapeutic effect of oleanolic acid (OA) on an accepted experimental model of MS, the experimental autoimmune encephalomyelitis (EAE). We have found that OA treatment, before or at the early onset of EAE, ameliorates neurological signs of EAE-mice. These beneficial effects of OA seem to be associated with a reduction of blood–brain barrier leakage and lower infiltration of inflammatory cells within the CNS, as well as with its modulatory role in Th1/Th2 polarization: inhibition of proinflammatory cytokines and chemokines, and stimulation of anti-inflammatory ones. Moreover, EAE-animals that were treated with OA had lower levels of anti-MOG antibodies than untreated EAE-mice. Our findings show that the administration of the natural triterpenoid OA reduces and limits the severity and development of EAE. Therefore, OA therapy might be of clinical interest for human MS and other Th1 cell-mediated inflammatory diseases., This work was supported by the Ramon y Cajal Program (to M.H.), F.P.I. Program from the Autonomous Government of Castilla y Leon (to R.M.) both co-funded by F.S.E., Grants SAF2005-01242 and SAF2008-00245 from the Spanish Ministry of Science and Technology, and Grant CSI11A08 from the Autonomous Government of Castilla y Leon.

Publisher Summary Hypertension (high blood pressure) is a major risk factor for cardiovascular disease. Hypertensive individuals have a higher risk of developing coronary heart disease, heart failure, stroke and kidney disease. In addition to its harmful effect on cardiovascular disease and mortality, hypertension is highly prevalent. In Western Europe, more than 40% of the adult population can be considered hypertensive. Both factors make hypertension a major public health problem. Different studies have shown that, in addition to genetic factors, both dietary and non-dietary factors can influence the risk of developing hypertension. Thus, excessive weight, lack of physical activity, excessive consumption of alcohol and sodium, and a low intake of potassium are factors that have been consistently found to increase the risk of hypertension. Similarly, interventions aimed to tackle these risk factors have been shown to be effective in the prevention and treatment of hypertension. Despite our considerable knowledge on the association between diet and hypertension, some unanswered questions remain. Most studies evaluating the association between diet and risk of hypertension have been conducted in the United States and northern Europe, regions with specific dietary patterns. The role of foods less represented in these populations in the prevention of hypertension, such as olive oil, is less clear.

Publisher Summary Virgin olive oil, as the main fat source of the Mediterranean diet, has been proposed as one of the healthiest dietary oils, since there is increasing evidence demonstrating beneficial effects on the pathophysiology of atherosclerosis. Certainly, a number of experimental studies have revealed that virgin olive oil consumption can have favorable effects on hypercholesterolemia and hypertension. Traditionally the beneficial effect of virgin olive oil was ascribed to its fatty acid composition and the high monounsaturated fatty acid content. However, it has been demonstrated that minor components also have a very relevant role. In this regard, second-centrifugation pomace olive oil is particularly rich in some minor components with an elevated biological activity. Despite being devoid of polyphenols, the concentration of sterols and tocopherols is higher in pomace olive oil. In addition, pomace olive oil contains relevant amounts of triterpenic compounds, like the oleanolic and maslinic acids and the erythrodiol and uvaol alcohols, which have been related with the improvement in endothelial dysfunction in hypertensive animals. Although there is still a lack of clinical studies, pomace olive oil is emerging as a healthy dietary oil, with important implications in endothelial dysfunction, one of the first events occurring during the development of atherosclerosis.

Publisher Summary Among olive and pomace olive oil triterpenoids, oleanolic acid has been the most widely studied and distributed in the vegetable kingdom. In fact, a wide range of biological activities has been attributed to this triterpenoid. Nevertheless, there are not many studies focused on the cardiovascular properties ascribed to oleanolic acid and structure-related triterpenoids such as erythrodiol. Accordingly, parenteral administration of this triterpenic acid lowers blood pressure in salt-sensitive rats, an effect mainly associated with antioxidative actions. In addition, it has been recently reported that ingestion of pomace olive oil with a high proportion of oleanolic acid and erythrodiol offers a delay in the progression of lipid peroxidation in rat liver microsomes. Despite these recent findings, the effects of oleanolic acid and pomace olive oil on vascular and endothelial function have remained unknown until now. This chapter summarizes the recent and novel advances in the vasoprotective profile provided by olive and pomace olive oil and their triterpenoids in terms of vasodilatation.

The hypothesis that the maslinic acid (MA) of olive oil (OO) dramatically influences hepatic gene expression was tested in mice. Two OOs only differing in the presence of MA were prepared. Using DNA microarrays, we analyzed hepatic gene expression in apolipoprotein E (apoE)-deficient mice with a C57BL/6J genetic background that were fed with isocaloric, isonitrogenous diets containing either 10% (w/w) OO or 10% MA-enriched OO. As an initial screening of potential candidate genes involved in a differential response, this study further considered only genes with remarkably modified expression (signal log2 ratio higher than1.5 or lower than −1.5). The nine genes fulfilling these prerequisites were confirmed by quantitative reverse transcriptase polymerase chain reaction and analyzed in C57BL/6J wild-type mice. Only Cyp2b9, Cyp2b13 and Dbp expressions appeared significantly increased, and Marco was significantly decreased in apoE-deficient mice receiving the MA-enriched diet. Dbp was up-regulated to an extent depending on the genetic background of the mice and negatively associated with the expression of Marco, a gene strongly up-regulated by the absence of apoE. These expression changes could be used as markers of the intake of the MA-enriched OO and are influenced by genetic background generated by the absence or the presence of apoE. Overall, these results (a) indicate that MA in virgin OO is highly active in controlling hepatic gene expression and (b) highlight the important interaction between the response to MA and the presence of apoE. They also confirm that virgin OO cannot be simplistically classified as monounsaturated fatty-enriched oil without paying attention to its active minor components., This research was supported by grants from FEDER-CICYT (SAF2007-60173, AGL2005-00572 and AGL2008-02285/ALI), Redes DGA (B-69) and FISS de Investigación Cooperativa (C03-01 and G03-140) and by Fundación Española del Corazón and Instituto Aragonés de Ciencias de la Salud. S.A. and N.G. were recipients of DGA and Fundación Cuenca Villoro fellowships.

Pomace olive oil is a by-product of olive oil extraction that is traditionally produced and consumed in Spain. The nonglyceride matter of this oil is a good source of interesting minor compounds, like long-chain fatty alcohols, which are present free or as part of waxes. In the present study, long-chain fatty alcohols were isolated from the nonglyceride fraction of pomace olive oil, and the composition was identified and quantified. The major components of long-chain fatty alcohols were tetracosanol, hexacosanol and octacosanol. We investigated the ability of long-chain fatty alcohols from pomace olive oil to inhibit the release of different proinflammatory mediators in vitro by cells involved in inflammatory processes. Long-chain fatty alcohols significantly and dose-dependently decreased nitric oxide production by RAW 264.7 murine macrophages stimulated with lipopolysaccharide. Western blot analysis showed that nitric oxide reduction was a consequence of the inhibition of inducible nitric oxide synthetase expression. Long-chain fatty alcohols also reduced tumor necrosis factor-α and prostaglandin E2 production, although the potency of inhibition for the latter was lower. On the other hand, long-chain fatty alcohols significantly reduced thromboxane A2 production in rat peritoneal neutrophils stimulated with the calcium ionophore A-23187. The reduction of eicosanoid release was related to the inhibition of phospholipase A2 enzyme activity by long-chain fatty alcohols, reaching an inhibitory concentration 50% value of 6.2 μg/ml. These results showed that long-chain fatty alcohols may have a protective effect on some mediators involved in the inflammatory damage development, suggesting its potential value as a putative functional component of pomace olive oil., This study was supported by funds from “Comision Interministerial de Ciencia y Tecnologia “(CICYT AGL2002-00195 and AGL2005-00572).

Epidemiological, clinical and experimental studies suggest that the cardioprotective effect of fish intake is mainly due to the antiarrhythmic properties of marine n-3 polyunsaturated fatty acids (PUFA), which modulate ion currents. Emerging evidences point to similar effects of alpha-linolenic acid (ALA), a vegetable n-3 PUFA, but much less is known about its effects on the specific cardiac ion channels. Using electrophysiology, protein biochemistry and fluorescence anisotropy measurements, we tested the effects of ALA on the atrial specific Kv1.5 channel. In stably transfected Ltk(-) cells, ALA blocked Kv1.5 channels in a time- and voltage-dependent manner with an IC(50) value of 3.7+/-0.3 microM. ALA at 2.5 microM inhibited the Kv1.5 current, shifted the midpoint of the activation curve by -8.8+/-4.3 mV (p

BACKGROUND: Squalene is an intermediate of cholesterol biosynthesis which can be obtained from the diet where it is abundant, for example, in olive oil. The effect of this isoprenoid on the development of atherosclerosis was investigated on apoE-knockout mice. METHODS AND RESULTS: Two groups of animals, separated according to sex, were fed on standard chow diet: the control group receiving only vehicle and the second group an aqueous solution of squalene to provide a dose of 1g/kg/day in male and female mice. This treatment was maintained for 10 weeks. At the end of this period, plasma lipid parameters, oxidative stress markers and hepatic fat were measured as well as cross-sectional lesion area of aortic root in both groups. Data showed that in males squalene feeding reduced atherosclerotic lesion area independently of plasma lipids and activation of circulating monocytes. In contrast, squalene intake did not decrease lesion area in females, despite reducing plasma cholesterol and triglycerides, isoprostane and percentage of Mac-1 expressing white cells. In males, atherosclerotic lesion area was positively and significantly associated with hepatic fat content and the plasma triglycerides were also strongly associated with liver weight. CONCLUSIONS: These results indicate that administration of squalene modulates lesion development in a gender specific manner, and that accumulation of hepatic fat by liver is highly correlated with lesion progression in males. Hence, squalene administration could be used as a safe alternative to correct hepatic steatosis and atherosclerosis particularly in males.

Background & aims: Hypertension is one of the most important risk factors for coronary heart disease. Recent studies have pointed out the possibility that virgin olive oil (VOO) may lower blood pressure in hypertensive (HT) subjects. However, until the date there is scarce information regarding elderly people. The present study was designed to assess the effect of dietary VOO on blood pressure in medically treated hypertensive elderly patients. Methods: 31 medically treated HT elderly patients and 31 normotensive (NT) elderly volunteers participated in a randomized sequential dietary intervention. Subjects consumed diets enriched in sunflower oil (SO) or VOO for 4 weeks each with a 4-week washout period between them. Results: VOO reduced total and LDL-cholesterol in NT but not in HT (P, This work was supported by FEDER funds from the European Community (FEDER 1FD97-2288) and from Junta de Andalucia (CAO 01-002).

Virgin olive oil (VOO) compared with fish oil (FO) and evening primrose oil (PO) on the ability of stimulated leukocytes to produce inflammatory mediators was investigated in rats. Weaned Wistar rats were fed a basal diet (BD) (2% by weight of corn oil) or diets containing 15% by weight of VOO, PO, or FO. After 8 weeks, glycogen-elicited peritoneal polymorphonuclear leukocytes, mainly neutrophils, were isolated. The calcium-ionophore stimulated neutrophils (2.5 x 10(6) cells/mL) obtained from rats fed the different oils produced a higher release of lysosomal enzymes (beta-glucuronidase, lysozyme, and myeloperoxidase [MPO]) compared with those fed BD. The production of reactive oxygen species (ROS) in response to the stimulant, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), by neutrophils from the VOO group (15.44 nmol of O(2)(-) and 6.56 nmol of H(2)O(2)) was similar to the BD group (12.01 nmol O(2)(-) and 8.49 nmol H(2)O(2)) and significantly lower than the PO (20.90 nmol O(2)(-) and 10.84 nmol H(2)O(2)) and FO (20.93 nmol O(2)(-) and 12.79 nmol H(2)O(2)) groups. The cyclooxygenase-derived eicosanoid production was reduced by the lipid enrichment of the diets. Whereas the generation of prostaglandin E(2) (PGE(2)) was significantly decreased in VOO (5.40 ng/mL), PO (4.95 ng/mL), and FO (1.44 ng/mL) groups compared with BD (8.19 ng/mL), thromboxane B(2) (TXB(2)) reduction was especially significant in neutrophils from the FO diet group (14.67 ng/mL compared with 26.69 ng/mL from BD). These experimental data suggest that FO and PO, as well as VOO, could be considered a valuable strategy in preventing the generation of some inflammatory mediators.

The major phenolics from the polar fraction of virgin olive oil (caffeic acid, oleuropein, tyrosol and hydroxytyrosol) have well-established antioxidant activities but their effects on reactive nitrogen species and nitrergic neurotransmission have not been fully investigated. The three catechol compounds were active as scavengers of nitric oxide generated spontaneously from the decomposition of sodium nitroprusside (approximately 50% inhibition achieved at 75 microM), and had similar ability to scavenge chemically generated peroxynitrite, as determined by an alpha1-antiproteinase inactivation assay (67.2%-92.4% reduction when added at 1 mM). Tyrosol was less active in these tests, but does not possess the catechol functionality. Despite their ability to interact with chemically prepared nitric oxide, neither oleuropein nor hydroxytyrosol at 5 microM altered NO*-mediated relaxations of the nerve-stimulated rat anococcygeus preparation, but this may be because the nitrergic transmitter is protected from the effects of externally applied scavengers. In conclusion, the phenolics found in virgin olive oil possess ability to scavenge reactive oxygen and nitrogen species that are implicated in human pathologies, but their impact may be restricted to those species present in the extracellular environment., We thank the “Comisión Interministerial de Ciencia y Tecnología” (CICYT) and the “Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria” (INIA) for partial financial support of this work ( Projects ALI99-0863 and CAO99-006 respectively).

Despite having similar fatty acid composition and plasma lipid composition after ingestion, olive oil, but not high-oleic sunflower oil (HOSO), is capable of reducing blood pressure. HOSO contains mainly triolein, whereas olive oil contains important amounts of dioleoyl-palmitoyl-glycerol. In order to see if its different triacylglycerol (TAG) composition could be related to the hypotensive effect of olive oil, Spontaneously Hypertensive Rats (SHR) were fed with HOSO and olive oil-rich diets. Liver lipid composition was determined. Total lipid, fatty acid and TAG composition was analyzed. Rats fed olive oil (67.24 ± 4.23) were observed to retain more dioleoyl-acyl-glycerol species in their liver than those fed HOSO (56.6 ±3.95), specially triolein (20.69 ± 1.77 olive oil, vs. 12.54 ± 1.97 HOSO), in spite of its lower content of this TAG. On the contrary, rats consuming HOSO had higher amounts of dilinoleoyl-acyl-glycerol species (9.26 ± 1.57 HOSO, vs.4.02 ± 0.90 olive oil). In conclusion, olive oil provided a more beneficial TAG profile in the liver of SHR rats than HOSO, probably due to the differences in the TAG composition of both oils.

Olive oil, but not high-oleic sunflower oil, is known to decrease blood pressure levels in patients with essential hypertension. Differences have been found in the minor component and triacylglycerol (TAG) contents. In order to determine whether differences are found in the content of liver lipids after administration of two monunsaturated oils from distinct sources, Wistar rats were fed with olive oil or high-oleic sunflower oil. Both oleic acid-rich oils caused similar effects on liver total lipids, phospholipids and cholesterol. When olive oil was administered to rats, the liver fatty acid content was also very similar to that of rats receiving high-oleic sunflower oil. However, olive oil intake resulted in a greater amount of dioleoylacylglycerol molecular species in rat liver, suggesting an increase in these species synthesis. This effect was not observed in rats consuming high-oleic sunflower oil, although the liver triacylglycerol pool was as high as that of rats receiving olive oil., Supported by grants (ALI96-0456 and OLI96-2126) from Comision Interministerial de Ciencia y Tecnologla (CICYT) and by a fellowship from the Gobiemo Vasco. We are grateful to M” Fernanda Leone and Manuel Rodriguez Aguilar for performing the analysis and excellent technical assistance

The free diacylglycerols (DAGs) in adipose tissue are involved in the metabolism of stored lipids and hence are related to the supply of fatty acids for other tissues. This paper describes a simple, fast, and reproducible method for the identification and quantification of different molecular species of DAGs in human adipose tissue. The method comprised solid-phase extraction on a diol-bonded phase column combined with capillary GC analysis of silylated DAG derivatives on a polar phase (65% phenylmethylsilicone). Separation of the DAGs was achieved based on chain length, isomeric structure (1,2- and 1,3-DAGs), and degree of unsaturation. The main DAGs were 1,2-OO, 1,2-OP, 1,2-LO and 1,2-LP. The composition was corroborated by analysis of the component fatty acids of the DAGs, 18:1(n-9), 16:0, and 18:2(n-6) being the three major fatty acids obtained., This study was supported by grants ALI 96-0456 and OLI 96-2126 from the Comisión Interministerial de Ciencia y Tecnologı́a (CICYT).

This study has been undertaken to determine the effect of a diet enriched with olive oil (OO) and high-oleic sunflower oil (HOSO) on fatty acid composition of erythrocyte membrane phospholipids and blood pressure in healthy women. OO and HOSO were used as natural sources of monounsaturated fatty acids (MUFAs) in a random-order sequence over two 4-week periods with a 4-week washout period between both MUFA diets. HOSO diet resulted in significant increases in oleic [(18:1n-9) 8.6%, P < 0.001], eicosenoic [(20:1n-9) 33.3%, P < 0.05], arachidonic [(20:4n-6) 6.2%, P < 0.05], and docosapentaenoic [(22:5n-6) 56.0%, P < 0.001] acids, whereas OO diet besides increased the content of stearic acid [(18:0) 13.6%, P < 0.01] and long-chain polyunsaturated fatty acids (PUFAs) of the n-3 family (22:5n-3 and 22:6n-3), when compared with the baseline [a diet high in saturated fatty acids (SFAs) and low in MUFAs]. In contrast, there was a significant decrease in linoleic acid [(18:2n-6) 21.8%, P < 0.001] for both MUFA diets. Consistent with these data, dietary intake of OO significantly raised total PUFAs (7.2%, P < 0.05), the n-3 fatty acids (22.2%, P < 0.01) and the ratio (9.3%, P < 0.01), as well as decreased the ratio of cholesterol to phospholipids (26,1%, P < 0.001) versus HOSO-based diet. Interestingly, dietary OO, but not HOSO, was able to significantly reduce the systolic (3%, P < 0.05) and diastolic (4%, P < 0.05) blood pressures. Although both vegetable oils provided a similar content of MUFAs (mainly oleic acid), our findings rather indicate that OO has important benefits to modulate the fatty acid composition of membranes and the mechanisms involved in the regulation of blood pressure in human.

Olive oil (OO) and high-oleic sunflower oil (HOSO) were employed as a natural sources of monounsaturated fatty acids (MUFAs) over two 4-wk periods, during which each twelve participants ate OO or HOSO diets, with a 4-wk washout period between the two MUFA diets. Plasma low-density-lipoprotein (LDL) cholesterol decreased (P < 0.05) by 9 and 6 % after OO and HOSO diets respectively. There was a significant increase of 18 % (P < 0.01) after OO diet and 12 % (P < 0.05) after HOSO diet in plasma high-density-lipoprotein (HDL) cholesterol. A significant decrease in plasma HDL2-cholesterol and an increase in plasma HDL3-cholesterol were also evident either after OO or HOSO diets. Free and esterified cholesterol decreased by 20 % (P < 0.01) and 41 % (P < 0.001) respectively in erythrocyte membrane after OO diet, but did not after HOSO diet. Erythrocyte phospholipids were also increased by 10 % (P < 0.01) after OO diet, and in turn diminished the molar ratio of cholesterol to phospholipids in the membrane. These data demonstrate that the beneficial effects of dietary OO in reducing the atherogenic risk profile in healthy subjects are not equally found after HOSO-rich diet, although both vegetable oils provide a similar concentration of MUFAs., We also gratefully acknowledge the technical assistance of Femanda Leone and Manuel Rodriguez, and the support of the Department for Food Analysis at the Instituto de la Grasa (CSIC).

The effects of olive oil (OO)- and high-oleic sunflower oil (HOSO)-enriched diets on erythrocyte membrane cholesterol distribution (by means of cholesterol oxidation after continuous cholesterol oxidase treatment) and Na+Li+ countertransport activity in control subjects and patients with untreated essential hypertension (with or without concomitant hypercholesterolemia) have been examined. The participants were 12 normotensive and sixteen hypertensive women who consumed in randomized order the two monosaturated fatty acid (MUFA) diets over 4-week periods separated by a 4-week washout period. The half-times for cholesterol oxidation were significantly higher in hypertensive women, ranging from an increase of 38 to 57% in the normo-(20.6 ± 2.8 min; P < 0.001) and hyper-(23.4 ± 4.2 min; P < 0.001) cholesterolemic groups. There was a general decrease by 75% in the half-time for cholesterol oxidation after HOSO diet. Interestingly, the oxidation rates were almost normalized after OO diet. The activity of Na+Li+ countertransport was found to be significantly higher in hypertensive women, ranging the increase from 22 to 57% in the normo-(0.314 ± 0.043 mmol × [h × liter cell]−1; P < 0.01) and hyper-(0.405 ± 0.086 mmol × [h × liter cell]−1; P < 0.01) cholesterolemic groups. This transport system was further activated after HOSO diet, while almost restored after OO diet. These findings suggest that dietary OO, but not HOSO, is helpful for normalizing the impaired distribution of membrane cholesterol and reducing elevated activity of Na+Li+ countertransport in erythrocyte of hypertensive patients. This action of OO also indicates that alterations in membrane cholesterol distribution may be relevants for the pathogenesis of hypertension. The effects, however, cannot be exclusively attributed to the content of MUFAs (mainly oleic acid) in the diet, as HOSO was unable to induce favorable changes.

alpha-Fetoprotein (AFP) is an oncofetal antigen believed to play an important role in normal development and carcinogenesis but very little is known about such a role. We have investigated here the role of AFP in neural retina development by selectively neutralising AFP in vitro. AFP has been immunohistochemically located in different cells and layers of the retina during its development, 4-day-old embryos being the earliest developmental stage when AFP is detected in the growing ganglion cell layer. Seven-day-retinae treated with antibodies to AFP in organ culture for 3 days did not continue to develop in the same way that they do in the egg. Neither the plexiform layers nor the buds of photoreceptor cells were observed after this culture period. In contrast, 7-day retinae cultured in the presence of non-immune serum developed in a manner similar to retinae in ovo. We present here the first evidence, derived by selectively blocking AFP in vitro with specific antibodies for an essential role of AFP in the normal development of the chick retina.

Hypertension is associated with some abnormalities in cell membrane structure, including an impaired distribution of cholesterol into the monolayers of erythrocyte membrane. Transbilayer movement of membrane cholesterol modulates the formation of these structural cholesterol domains. We tested whether the rate of cholesterol movement may influence on the erythrocyte Na+-Li+ countertransport, that is a marker of human essential hypertension. In single regression analysis, the half-time for the decrease in specific radioactivity of cholestenone (inverse of membrane cholesterol transbilayer movement) was negatively related to the erythrocyte cation flux mediated by Na+-Li+ countertransport (r = -0.8983, P, Supported by a grant (AL1950073) from Comision Interministerial de Ciencia y Tecnologia (CICYT), and the Andalusian Heart Service.

This article discusses the methods most commonly employed in the analysis of the triacylglycerols (TAGs) in natural fats and considers the main advantages and disadvantages of each and the techniques for optimising analytical conditions. Complete analysis of the composition of a natural fat calls for a method of extracting and purifying the triglyceride fraction, normally by preparatory thin-layer and column chromatography. Determination of the individual components of triglyceride mixtures still entails certain difficulties, namely, the separation and identification of the TAGs in natural fats. High-performance liquid chromatography (HPLC) offers significant advantages over gas and thin-layer chromatography. Many workers have developed non-aqueous, reversed-phase HPLC systems capable of successfully resolving complex mixtures of TAGs, and combining reversed-phase (RP) HPLC and argentation chromatography may improve the results. Identification of the TAGs separated by HPLC becomes an extremely complex task if many different fatty acids are involved and if the sn-stereoscopic positions on the glycerol are to be determined. Enzymatic analysis and chiral-phase chromatography are capable of localising fatty acids on the TAG molecule. In closing, some of the most interesting biomedical applications of TAG analysis are summarised.

Brush-border membrane vesicles (BBMV) were isolated from prawn hepatopancreas as we previously described (Muriana et al (1993) J Biochem 113, 625–629). The characterization of hepatopancreatic BBMV (hBBMV) by monitoring the activity of marker enzymes indicated a relatively pure apical membrane preparation reduced in basolateral contamination. Phospholipid composition of hBBMV was examined by the Iatroscan TLC/FID technique, whereas the fatty acid profile of phospholipids was examined by capillary gas chromatography. Phosphatidylcholine and phosphatidylethanolamine are the principal phospholipids of these membranes. The major fatty acids of phospholipids are palmitic (16:0), palmitoleic (16:ln-7), stearic (18:0), oleic (18:ln-9), eicosapentaenoic (20:5n-3) and docosapentaenoic (22:5n-3) acids. Individual phospholipids are characterized by distinct fatty acid composition, but display a similar ratio of unsaturated-to-saturated fatty acids and a similar unsaturation index., This work was supported by a Grant from the Comisión de Investigación Científica y Técnica (MAR 89-03411.

Male rats of the Wistar strain were given oleuropein for 3 weeks at a dose of 25 or 50 mg/kg of body weight. Heart samples were analyzed for the lipid composition by the Iatroscan TLCFID technique and for the fatty acid profile of neutral and polar lipids by the capillary gas chromatography. In addition, the oleuropein, α- and β-tocopherol content in the total heart lipids were also determined. Oleuropein treatment increased the level of cholesteryl esters, but it decreased the level of triacylglycerols, in the heart of animals. Sphingomyelin and lysophosphatidylcholine levels were only higher in the 50 mg oleuropein group. There was also a significant reduction in the linoleic acid content in the heart polar lipids of oleuropein-treated animals. As consequence of treatment, oleuropein was incorporated into the heart of animals in a concentration-dependent manner, whereas the α- and β-tocopherol content decreased. Oleuropein may therefore act as a substitute of the natural antioxidants in heart, with minor changes in the unsaturated lipids.

The fatty acid composition of human very-low-density lipoproteins (VLDL) was studied in a population from western Andalusia with a diet in which the fat content came mainly from olive oil. The lipid composition of VLDL, including the fatty acid composition of the phospholipids and triacylglycerols, was examined by capillary gas chromatography. Twenty-five peaks were resolved, ranging in chain length from 14 to 24 carbon atoms, including geometric and positional isomers. The major fatty acids present in phospholipids were 16:0, 18:0, 18:1(n − 9) and 18:2(n − 6), and in triacylglycerols were 18:1(n − 9), 16:0 and 18:2(n − 6). The major triacylglycerol was POO, followed by PLO and OOO. MLP, PPS and LLL were absent. The presence of a large amount of OOO in this fraction demonstrates that the triacylglycerol composition of the VLDL depends on the type of diet consumed., This work was supported by a grant from the Comisión Interministerial de Ciencia y Tecnología.

The effect of aging on the lipid composition and fluidity of rat peritoneal macrophage membranes has been determined using young (3 months), mature (12 months) and aged (24 months) Wistar rats. In the aged animals, total phospholipid decreased significantly (P < 0.05), whereas cholesterol increased (P < 0.01), with an age-dependent increase in the molar ratio of cholesterol/phospholipid. The most marked change in phospholipid content was the significant (P < 0. 001) age-dependent increase of phosphatidylserine and cardiolipin and the significant decrease of phosphatidylcholine and phosphatidylinositol. During aging there was a considerable decrease in arachidonic acid and docosapentanoic acid (about 50% in both cases). In contrast, an increase in the levels of oleic, linolenic and docosahexanoic acid was observed. Steady-state fluorescence polarization using 1,6-diphenyl-l,3,5-bexatriene as the probe was used to estimate the lipid structural order parameter of macrophage membranes. There was a highly significant (P < 0.001) age-dependent increase in the lipid structural order parameter, which correlated well with the increased molar ratio of cholesterol/ phospholipid in the membranes isolated from aged animals. The data suggests alteration in membrane lipid-protein interactions in aging, and are consistent with the hypothesis of the aging process., Eloisa Alvarez is a recipient of a fellowship from the Junta de Andalucia. This work was supported by grant PB89-0173 from CAI de Ciencia y Tecnologia.

The lipid composition of rat caecal mucosa, including the fatty acid composition of phospholipids and triacylglycerols, has been examined by capillary gas chromatography. Thirty-seven peaks were resolved, ranging in chain length from 12 to 24 carbon atoms. Preliminary identification of fatty acids by comparison with authentic standards was confirmed by gas chromatography—mass spectrometry using electron-impact ionization. The neutral and polar components were examined. Fatty acid methyl esters were quantified in absolute amounts with respect to the percentage of total phospholipid and triacylglycerols. The results show significantly higher levels of 16:0, 18:0, 18:1(n − 9), 18:1(n − 7), 18:2(n − 6) and 20:4(n − 6) in phospholipids, and higher levels of 16:0, 18:1(n − 9) and 18:2(n − 6) in triacylglycerols. On the other hand, analysis of caecal triacylglycerols revealed sn-glycerol-palmitate-oleate-palmitate, sn-glycerol-palmitate-linoleate-palmitate and sn-glycerol-palmitate-linoleate-oleate as major components.

In this study, we examined the lipid composition of rat caecal mucosa, including the fatty acid composition of major phospholipid classes. Phospholipids accounted for 90% of the total lipid, with cholesterol, triacylglycerols, diacylglycerols, fatty acids and cholesterol ester making up the remainder. Therefore, a phospholipid to neutral lipid ratio of 9:1 was found. Phosphatidylethanolamine was the predominant phospholipid, with phosphatidylcholine as the second most abundant phospholipid. Cardiolipin, phosphadidylserine, phosphatidylinositol and lysophosphatidylcholine were present in lesser amounts. Sphingomyclin and lysophosphatidylethanolamine were only detected in trace amounts. The major fatty acids present in both the lipid and all phospholipid fractions were palmitate, stearate, oleate, linoleate and arachidonate. Other fatty acids of chain length greater than C20 were only detected in phospholipid fraction and accounted for

Fresh and thermally oxidized olive and sunflower oils were fed to rats at a practical level of concentration. Rats were fed a diet ad libitum for 10 months that contained 12% (wt/wt) of a test oil. Fatty acid composition of liver microsomes; physical state of the membrane lipids; and activities of the Δ 9 , Δ 6 , and Δ 5 desaturases were determined. The results demonstrate that dietary heated oils produce alterations in the desaturase activities of rat liver microsomes with concomitant changes in fatty acid composition of these membranes. Dietary heated oils accelerate the conversion of palmitic to palmitoleic acid by activating the Δ 9 desaturase activity and slow down the synthesis of arachidonic from linoleic acid by inhibiting the Δ 6 and Δ 5 desaturase activities in the rat liver microsomes. Fluorescence polarization studies, using diphenylhexatriene as a probe, showed lower membrane fluidity in olive oil groups than in sunflower oil groups. Moreover, there were significant differences between physical states of the membrane lipids from each group of the heated and non-heated oils. We concluded that thermally oxidized oils appear to produce alterations at the molecular level in the microsomes of rats, which are dependent on the composition of dietary lipids.

The influences of diets having different fatty acid compositions on the fatty-acid content, desaturase activities, and membrane fluidity of rat liver microsomes have been analyzed. Weanling male rats (35–45 g) were fed a fat-free semisynthetic diet supplemented with 10% (by weight) marine fish oil (FO, 12.7% docosahexaenoic acid and 13.8% eicosapentaenoic acid), evening primrose oil (EPO, 7.8% γ-linolenic acid and 70.8% linoleic acid) or a mixture of 5% FO-5% EPO. After 12 weeks on the respective diets, animals fed higher proportions of (n-3) polyunsaturated fatty acids (FO group) consistently contained higher levels of 20:3(n-6), 20:5(n-3), 22:5(n-3), and 22:6(n-3), and lower levels of 18:2(n-6) and 20:4(n-6), than those of the EPO (a rich source of (n-6) polyunsaturated fatty acids) or the FO + EPO groups. Membrane fluidity, as estimated by the reciprocal of the order parameter SDPH, was higher in the FO than in the EPO or the FO + EPO groups, and the n-6 fatty-acid desaturation system was markedly affected.

The serum lipid composition and the fatty-acid profiles of the major lipid fraction (triglycerides, esterified cholesterol, and phospholipid) of liver and serum were examined 6 weeks after both 50% and 75% distal small bowel resection (DSBR). Total serum lipid content did not modify after DSBR. Esterified cholesterol and phospholipid levels of the serum did not significantly change after the operation. However, a significant increase in both free cholesterol and triglyceride levels was observed after DSBR. Different fatty acid changes in the liver and serum lipid fractions were found after DSBR, with the greatest differences in the hepatic esterified cholesterol fraction. These results suggest that DSBR affects both the lipid composition and the fatty acid composition of major lipid fraction of liver and serum., This work was supported by a grant from the "Comisión Asesora de Investigación Científica y Técnica" (PB 85-0331).

1. 1. The acyl-CoA: cholesterol acyltransferase (ACAT) activity and lipid composition of intestinal microsomal membrane were investigated 6 weeks after both 50 and 75% distal small bowel resection (DSBR). 2. 2. No changes in both microsomal ACAT activity and cholesteryl ester levels were found, while microsomal non-esterified cholesterol content was increased after the surgical operation. 3. 3. The total phospholipid content of the microsomes did not change as a results of DSBR. 4. 4. The microsomal phospholipid fatty acid composition showed a significant increase in saturated fatty acids together with no changes in both total monounsaturated and total polyunsaturated fatty acids after resection. 5. 5. An increase in the levels of linoleic acid accompanied by a decrease in arachidonic acid was found in remnant intestine of resected rats.