Identification of linoleic acid as an antithrombotic component of Wenxin Keli via selective inhibition of p-selectin-mediated platelet activation.

Atrial fibrillation significantly increases the risk of thromboembolism and stroke. Wenxin Keli (WXKL) is a widely used Chinese patent medicine against arrhythmia but if it has antithrombotic activity is unknown. Since platelet activation is a critical factor in thrombosis and the key target for many antithrombotic drugs, this study aims to demonstrate the antithrombotic efficacy of WXKL. In vitro platelet activation experiments showed that WXKL significantly inhibited platelet adhesion and aggregation. The potential active monomers in WXKL were screened by in silico prediction and in vitro platelet aggregation/adhesion assays. From WXKL chemical fractions and more than 40 monomers, linoleic acid (LA) was identified as the strongest antiplatelet compound. Oral administration of WXKL (1.2 g/kg/day) and LA (50 mg/kg/day) for 7 days significantly improved FeCl3-induced carotid thrombus formation in ICR mice without prolonging bleeding time. Flow cytometry showed that both WXKL and LA inhibited the release of p-selectin after platelet activation. ELISA showed that WXKL and LA also inhibited the expression of 6-Keto-PGF1α in plasma of mice with thrombus, but had no obvious effect on the expression of TXB2. WXKL inhibited platelet activation by broadly inhibiting the phosphorylation of protein kinase B (Akt), mitogen-activated protein kinases (MAPKs) and phospholipase C (PLC) ß3. In contrast, LA only inhibited the phosphorylation of PLCß3. In conclusion, WXKL and its active component LA showed good antiplatelet and antithrombotic efficacy in vivo and in vitro. Mechanistically, the multicomponent Chinese medicine WXKL acts on multiple targets in the platelet activation pathway whereas its active monomer linoleic acid acts specifically on phospholipase C ß3.

Potent in vitro Anti-mouth Cancer (KB) and Immunostimulating Activities of the Job's Tears (Coix lachryma-jobi Linn.) Seed Semi-purified Extract Cocktails Containing Linoleic Acid.

The crude methanolic and hexane extracts of non-cooked, steamed and roasted from three Job's Tears cultivars were prepared and further semi-purified by liquid-liquid extraction techniques and silica gel column. The six single semi-purified extracts (F1-F6) were combined as nine cocktails (CT1, CT6, CT8, CT13, CT14, CT21, CT24, CT25 and CT31) according to the IC50 values from the preliminary study and investigated for anti-proliferative and apoptotic induction on mouth cancer cell line (KB) and immunostimulating as well as antioxidative activities. The highest anti-proliferative activity was observed in CT13 showing the IC50 value of 0.53±0.45 µg/mL which was higher than 5-fluorouracil and doxorubicin of 20.34 and 1.60 times, respectively. CT1 which was the combination of F1-F6 and CT13 which was the combination of F4-F6 exhibited significant strong synergistic activity with the combination index value (CI) of 0.28. CT1 at 200 µg/mL showed the highest percentages of apoptotic cells (40.65±10.97%) with no necrotic cells, but lower than cisplatin (100 µg/mL) of 2.18 times. CT14 gave the highest immunostimulating activity with the phagocytosis percentage of 13.0±1.7%, but lower than lipopolysaccharide of 1.08 times. CT31 gave the highest free radical scavenging and metal chelating activities with the SC50 and MC50 values of 0.73±0.07 and 1.99±0.24 µg/mL, but lower than ascorbic acid and EDTA of 18.25 and 4.33 times, respectively. The linoleic acid contents related to anti-cancer activity were also examined by HPLC. This study has demonstrated that CT1 composing of F1-F6 at the percentage ratio of 0.71:2.06:81.38: 8.47:4.92:2.46 was the potential cocktails of the semi-purified extracts from the Job's Tears which can be further developed as a novel active compound for oral cancer treatment.

Randomized, clinical trial of RT001: Early signals of efficacy in Friedreich's ataxia.

BACKGROUND: RT001 is a deuterated ethyl linoleate that inhibits lipid peroxidation and is hypothesized to reduce cellular damage and recover mitochondrial function in degenerative diseases such as Friedreich's ataxia. OBJECTIVE: To evaluate the safety, pharmacokinetics, and preliminary efficacy of RT001 in Friedreich's ataxia patients. DESIGN/METHODS: We conducted a phase I/II double-blind, comparator-controlled trial with 2 doses of RT001 in Friedreich's ataxia patients (9 subjects each cohort). Subjects were randomized 2:1 to receive either RT001 (1.8 or 9.0 g/day), or a matching dose of nondeuterated ethyl linoleate as comparator for 28 days. The primary endpoints were safety, tolerability, and pharmacokinetic analysis. Secondary endpoints included cardiopulmonary exercise testing and timed 25-foot walk. RESULTS: Nineteen patients enrolled in the trial, and 18 completed all safety and efficacy measurements. RT001 was found to be safe and tolerable, with plasma levels approaching saturation by 28 days. One subject with a low body mass index experienced steatorrhea taking a high dose and discontinued the study. Deuterated arachidonic acid (a brain-penetrant metabolite of RT001) was found to be present in plasma on day 28. There was an improvement in peak workload in the drug group compared to placebo (0.16 watts/kg; P = 0.008), as well as an improvement trend in peak oxygen consumption (change of 0.16 L/min; P = 0.116), and in stride speed (P = 0.15). CONCLUSIONS: RT001 was found to be safe and tolerable over 28 days, and improved peak workload. Further research into the effect of RT001 in Friedreich's ataxia is warranted. © 2018 International Parkinson and Movement Disorder Society.

Phytochemical composition and in vitro anti-tumour activities of selected tomato varieties.

BACKGROUND: Previous studies indicated that tomato is a rich source of phytochemicals that act on different tumours. In this research, the phytochemical composition of selected tomato varieties was assessed by GLC and UHPLC/HPLC-MS, as well as their anti-tumour activities on HT-29 colorectal cancer cells. RESULTS: Significant differences were found among tomato varieties; lycopene was high in Racimo, phenolics in Pera, sterols in Cherry, and linoleic acid predominated in all varieties. The MTT and LDH assays showed significant time- and concentration-dependent inhibitory/cytotoxic effects of all tomato varieties on HT-29 cells. Furthermore, the joint addition of tomato carotenoids and olive oil to HT-29 cell cultures induced inhibitory effects significantly higher than those obtained from each of them acting separately, while no actions were exercised in CCD-18 normal cells. CONCLUSION: Tomato fruits constitute a healthy source of phytochemicals, although differences exist among varieties. In vitro, all of them inhibit colorectal cancer cell proliferation with Racimo variety at the top, and exercising a selective action on cancer cells by considering the lack of effects on CCD-18 cells. Furthermore, synergy was observed between olive oil and tomato carotenoids in inhibiting HT-29 cancer cell proliferation; conversely, phenolics showed no significant effects and hindered carotenoids actions. © 2016 Society of Chemical Industry.

Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM-X-SORB (LXS), an easily absorbable lipid matrix that enhances fat absorption, was evaluated in a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110 subjects (age 10.4 ±â€Š3.0 years) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (P = 0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, P ≤ 0.046), with a 6% increase in CFA (P < 0.01). LA increase was significant in LXS versus placebo (445 vs 42 nmol/mL, P = 0.038). Increased FA and LA predicted increased body mass index Z scores. In summary, the LXS treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status.

Effect of Pistacia lentiscus oil on experimental pulmonary fibrosis.

Background - Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by histopathological lesions in lung tissue. This is the most common and most severe idiopathic interstitial pneumonias. Current treatments are based on the combination of corticosteroids and immunosuppressants, but their effectiveness is still debated. Purpose of work - Testing the preventive effect of Pistacia Lentiscus oil, known for its antioxidant, anti-mutagenic and anti-proliferative effects, on a model of experimental lung fibrosis. Methods - Two groups of rats received an intratracheal injection of bleomycin (4.5 mg / kg). The first group, control (n = 20 rats), has received no treatment. The second group was treated with Pistacia Lentiscus oil (n = 20 rats) for 30 days before fibrosis induction, by daily gavage oil Pistacia Lentiscus oil (3,33ml / kg). This treatment was continued for 10 days. At the end of the experimental period, all rats were sacrificed and the lung tissue was examined histopathologically and immunostained for TGFß. Results - The chromatographic profile oil Pistacia Lentiscus oil shows the dominance of two fatty acids that are linoleic acid and palmitic acid representing respectively 70.57 and 24.67%. Our results also show a decrease in the distribution of TGFß both at the level of the inflammatory infiltrate and at the level of the pulmonary parenchyma histiocytes of rats treated with Pistacia Lentiscus oil compared with control rats. However, these changes are not accompanied by statistically significant changes of fibrosis score and inflammatory index. Conclusion - Our results are interesting to consider. Further studies using higher doses of Pistacia Lentiscus oil are important to conduct.

Preeclampsia prevention: a case-control study nested in a cohort / La prevención de la preeclampsia: un estudio de casos y controles anidado en una cohorte

Introduction: Preeclampsia is the main complication of pregnancy in developing countries. Calcium starting at 14 weeks of pregnancy is indicated to prevent the disease. Recent advances in prevention of preeclampsia endorse the addition of conjugated linoleic acid. Objective: To estimate the protective effect from calcium alone, compared to calcium plus conjugated linoleic acid in nulliparous women at risk of preeclampsia. Methods: A case-control design nested in the cohort of nulliparous women attending antenatal care from 2010 to 2014. The clinical histories of 387 cases of preeclampsia were compared with 1,054 normotensive controls. The exposure was prescriptions for calcium alone, the first period, or calcium plus conjugated linoleic acid, the second period, from 12 to 16 weeks of gestational age to labor. Confounding variables were controlled, allowing only nulliparous women into the study and stratifying by age, education and ethnic group. Results: The average age was 26.4 yrs old (range= 13-45), 85% from mixed ethnic backgrounds and with high school education. There were no differences between women who received calcium carbonate and those who did not (OR= 0.96; 95% CI= 0.73-1.27). The group of adolescents (13 to 18 yrs old) in the calcium plus conjugated linoleic acid was protected for preeclampsia (OR= 0.00; 95% CI= 0.00-0.44) independent of the confounder variables. Conclusions: 1. Calcium supplementation during pregnancy did not have preventive effects on preeclampsia. 2. Calcium plus Conjugated Linoleic acid provided to adolescents was observed to have preventive effect on Preeclampsia.

Introducción: La preeclampsia es la principal causa de mortalidad materna y bajo peso al nacer en países en vías de desarrollo. Empezar la suplementación de calcio en la semana 14 de gestación es indicada para prevenir la enfermedad. Recientes avances en prevención de preeclampsia han sugerido la suplementación de calcio y la combinación de calcio con ácido linoleico conjugado. Objetivo: Estimar el efecto protector de la suplementación de calcio (CC), comparado con la suplementación de calcio más ácido linoleico conjugado (CC+ALC) en mujeres embarazadas primigravidas con relación al desarrollo de preeclampsia. Métodos: Se realizó un estudio de casos y controles anidado en una cohorte retrospectiva de mujeres embarazadas primigravidas que asistieron al programa de control prenatal entre el año 2010 hasta el años 2014. La historia clínica de 387 casos de preeclampsia fueron comparadas con 1,054 controles en pacientes embarazadas primigestantes, normotensas. Las gestantes expuestas fueron consideradas como aquellas gestantes que recibieron solo calcio, en el primer periodo de evaluación, o calcio más ácido linoleico conjugado, segundo periodo de evaluación, desde las semanas 12 a la 16 del embarazo. Los posibles factores de confusión se controlaron admitiendo solo las primigestantes y estratificando, por edad, educación y grupo étnico de la paciente. Resultados: La edad promedio de las pacientes fue de 26.4 años (rango= 13-45), 85% con etnia mestiza y educación secundaria completa. La exposición a CC+ALC tuvo un efecto protector en las adolescentes (13 a 18 años) (OR= 0.00, IC 95%= 0.00-0.44; p= 0.005), mientras que la exposición a CC no modificó la incidencia de preeclampsia (OR= 0.96, IC 95%= 0.73-1.27; p= 0.82). Conclusiones: 1. La suplementación de solo calcio durante el embarazo no tuvo efecto preventivo para la preeclampsia, 2. La suplementación con calcio y ácido linoleico conjugado previno la aparición de preeclampsia en adolescentes.

Omega-3 PUFAs Lower the Propensity for Arachidonic Acid Cascade Overreactions.

A productive view of the benefits from omega-3 (n-3) nutrients is that the dietary essential omega-6 (n-6) linoleic acid has a very narrow therapeutic window which is widened by n-3 nutrients. The benefit from moderate physiological actions of the arachidonic acid cascade can easily shift to harm from excessive pathophysiological actions. Recognizing the factors that predispose the cascade to an unwanted overactivity gives a rational approach for arranging beneficial interactions between the n-3 and n-6 essential nutrients that are initial components of the cascade. Much detailed evidence for harmful cascade actions was collected by pharmaceutical companies as they developed drugs to decrease those actions. A remaining challenge is to understand the factors that predispose the cascade toward unwanted outcomes and create the need for therapeutic interventions. Such understanding involves recognizing the similar dynamics for dietary n-3 and n-6 nutrients in forming the immediate precursors of the cascade plus the more vigorous actions of the n-6 precursor, arachidonic acid, in forming potent mediators that amplify unwanted cascade outcomes. Tools have been developed to aid deliberate day-to-day quantitative management of the propensity for cascade overactivity in ways that can decrease the need for drug treatments.

Preeclampsia prevention: a case-control study nested in a cohort.

BACKGROUND: Preeclampsia is the main complication of pregnancy in developing countries. Calcium starting at 14 weeks of pregnancy is indicated to prevent the disease. Recent advances in prevention of preeclampsia endorse the addition of conjugated linoleic acid. OBJECTIVE: To estimate the protective effect from calcium alone, compared to calcium plus conjugated linoleic acid in nulliparous women at risk of preeclampsia. METHODS: A case-control design nested in the cohort of nulliparous women attending antenatal care from 2010 to 2014. The clinical histories of 387 cases of preeclampsia were compared with 1,054 normotensive controls. The exposure was prescriptions for calcium alone, the first period, or calcium plus conjugated linoleic acid, the second period, from 12 to 16 weeks of gestational age to labor. Confounding variables were controlled, allowing only nulliparous women into the study and stratifying by age, education and ethnic group. RESULTS: The average age was 26.4 yrs old (range= 13-45), 85% from mixed ethnic backgrounds and with high school education. There were no differences between women who received calcium carbonate and those who did not (OR= 0.96; 95% CI= 0.73-1.27). The group of adolescents (13 to 18 years old) in the calcium plus conjugated linoleic acid was protected for preeclampsia (OR= 0.00; 95% CI= 0.00-0.44) independent of the confounder variables. CONCLUSIONS: 1. Calcium supplementation during pregnancy did not have preventive effects on preeclampsia. 2. Calcium plus Conjugated Linoleic acid provided to adolescents was observed to have preventive effect on Preeclampsia.

INTRODUCCIÓN: La preeclampsia es la principal causa de mortalidad materna y bajo peso al nacer en países en vías de desarrollo. Empezar la suplementación de calcio en la semana 14 de gestación es indicada para prevenir la enfermedad. Recientes avances en prevención de preeclampsia han sugerido la suplementación de calcio y la combinación de calcio con ácido linoleico conjugado. OBJETIVO: Estimar el efecto protector de la suplementación de calcio (CC), comparado con la suplementación de calcio más ácido linoleico conjugado (CC+ALC) en mujeres embarazadas primigravidas con relación al desarrollo de preeclampsia. METODOS: Se realizó un estudio de casos y controles anidado en una cohorte retrospectiva de mujeres embarazadas primigravidas que asistieron al programa de control prenatal entre el año 2010 hasta el años 2014. La historia clínica de 387 casos de preeclampsia fueron comparadas con 1,054 controles en pacientes embarazadas primigestantes, normotensas. Las gestantes expuestas fueron consideradas como aquellas gestantes que recibieron solo calcio, en el primer periodo de evaluación, o calcio más ácido linoleico conjugado, segundo periodo de evaluación, desde las semanas 12 a la 16 del embarazo. Los posibles factores de confusión se controlaron admitiendo solo las primigestantes y estratificando, por edad, educación y grupo étnico de la paciente. RESULTADOS: La edad promedio de las pacientes fue de 26.4 años (rango 13-45), 85% con etnia mestiza y educación secundaria completa. La exposición a CC+ALC tuvo un efecto protector en las adolescentes (13 a 18 años) (OR= 0.00, IC 95%= 0.00-0.44; p= 0.005), mientras que la exposición a CC no modificó la incidencia de preeclampsia (OR= 0.96, IC 95% %= 0.73-1.27; p= 0.82). CONCLUSIÓN: 1. La suplementación de solo calcio durante el embarazo no tuvo efecto preventivo para la preeclampsia, 2. La suplementación con calcio y ácido linoleico conjugado previno la aparición de preeclampsia en adolescentes.

Linoleic acid derivative DCP-LA ameliorates stress-induced depression-related behavior by promoting cell surface 5-HT1A receptor translocation, stimulating serotonin release, and inactivating GSK-3ß.

Impairment of serotonergic neurotransmission is the major factor responsible for depression and glycogen synthase kinase 3ß (GSK-3ß) participates in serotonergic transmission-mediated signaling networks relevant to mental illnesses. In the forced-swim test to assess depression-like behavior, the immobility time for mice with restraint stress was significantly longer than that for nonstressed control mice. Postsynaptic cell surface localization of 5-HT1A receptor, but not 5-HT2A receptor, in the hypothalamus for mice with restraint stress was significantly reduced as compared with that for control mice, which highly correlated to prolonged immobility time, i.e., depression-like behavior. The linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) restored restraint stress-induced reduction of cell surface 5-HT1A receptor and improved depression-like behavior in mice with restraint stress. Moreover, DCP-LA stimulated serotonin release from hypothalamic slices and cancelled restraint stress-induced reduction of GSK-3ß phosphorylation at Ser9. Taken together, the results of the present study indicate that DCP-LA could ameliorate depression-like behavior by promoting translocation of 5-HT1A receptor to the plasma membrane on postsynaptic cells, stimulating serotonin release, and inactivating GSK-3ß.

Unsaturated fat intakes and mental health outcomes in young women from the Australian Longitudinal Study on Women's Heath.

OBJECTIVE: To determine if associations exist between a range of unsaturated fatty acid intakes and mental health outcomes. DESIGN: Cross-sectional data analysis of the Australian Longitudinal Study on Women's Health (ALSWH) Young Cohort Survey 3 that included the validated seventy-four-item Dietary Questionnaire for Epidemiological Studies FFQ, validated mental health scales and self-report questions on depression and anxiety. SETTING: Australia, 2003. SUBJECTS: A nationally representative sample of young Australian women (25-30 years) from ALSWH. The 7635 women with plausible energy intakes (>4·5 but <20·0 MJ/d) were included in the analyses. RESULTS: Adjusted logistic regression analyses found statistically significant associations between higher intakes of α-linolenic acid and decreased likelihood of depressive symptoms indicated by the ten-item Center for Epidemiological Studies Depression Scale (CESD-10; OR=0·77; 95% CI 0·60, 0·99; P=0·040) and the Short Form Health Survey (SF-36) mental health subscale (OR=0·73 95% CI 0·56, 0·96; P=0·024). Furthermore, higher intakes of n-6 fatty acids (OR=0·96, 95% CI 0·93, 0·99; P=0·019) and linoleic acid (OR=0·96, 95% CI 0·93, 0·99; P=0·020) were associated with decreased likelihood of self-reported diagnosed anxiety and higher intakes of n-9 fatty acids (OR=1·02, 95% CI 1·00, 1·04; P=0·041) and oleic acid (OR=1·02, 95% CI 1·00, 1·05; P=0·046) were associated with increased likelihood of self-reported diagnosed anxiety. CONCLUSIONS: Increased intakes of α-linolenic acid were associated with a reduced likelihood of depressive symptoms, increased intakes of n-6 fatty acids and linoleic acid were associated with a reduced likelihood of self-reported anxiety, and increased intakes of n-9 fatty acids and oleic acid were associated with an increased likelihood of anxiety. Additional studies are needed to further elucidate associations between unsaturated fatty acids and depression and anxiety.

In vivo hair growth-promoting effect of rice bran extract prepared by supercritical carbon dioxide fluid.

The potential hair growth-promoting activity of rice bran supercritical CO2 extract (RB-SCE) and major components of RB-SCE, linoleic acid, policosanol, γ-oryzanol, and γ-tocotrienol, were evaluated with the histological morphology and mRNA expression levels of cell growth factors using real-time reverse transcriptase-polymerase chain reaction (PCR) in C57BL/6 mice. RB-SCE showed hair growth-promoting potential to a similar extent as 3% minoxidil, showing that the hair follicles were induced to be in the anagen stage. The numbers of the hair follicles were significantly increased. In addition, mRNA expression levels of vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and keratinocyte growth factor (KGF) were also significantly increased and that of transforming growth factor-ß (TGF-ß) decreased in RB-SCE-treated groups. Among the major components of RB-SCE, linoleic acid and γ-oryzanol induced the formation of hair follicles according to examination of histological morphology and mRNA expression levels of cell growth factors. In conclusion, our results demonstrate that RB-SCE, particularly linoleic acid and γ-oryzanol, promotes hair growth and suggests RB-SCE can be applied as hair loss treatment.

Chia (Salvia hispanica) / Chia (Salvia hispanica)

Introdução: A chia é uma planta cujas sementes são utilizadas na culinária e dita com diversas propriedades medicinais.Objetivo: Verificar evidências do uso da chia no tratamento de doenças.Métodos: Busca sistematizada da literatura, por meio de busca eletrônica, de artigos que avaliem o uso da chia naterapêutica médica.Resultados: Uma revisão sistemática mostrou resultados inconclusivos da eficácia da chia no tratamento de doenças.Um ensaio clínico randomizado não conseguiu demonstrar benefício na redução de peso. Um estudo crossover nãoconseguiu demonstrar um efeito energético superior aos carboidratos em atletas. Dois estudos experimentais emanimais foram favoráveis à chia na redução de riscos cardiovasculares e em câncer. Um estudo mostrou efeito benéficodo óleo das sementes de chia no tratamento tópico do prurido em pacientes renais e diabéticos. Em todos os estudosnão há ocorrência de efeitos adversos.Conclusão: Chia não pode ser considerado um fitoterápico no tratamento isolado de qualquer doença ou com finalidadede perda de peso. Ela pode ser utilizada como complemento dietético.

Caenorhabditis elegans as a model to study the effectiveness and metabolic targets of dietary supplements used for obesity treatment: the specific case of a conjugated linoleic acid mixture (Tonalin).

The antiobesity effect of conjugated linoleic acid (CLA) has previously been described in different animal models. The aim of the present study was to investigate the effect of a commercial mixture (Tonalin) on Caenorhabditis elegans to assess their potential use for functional ingredient screenings. Body-fat reduction with Tonalin was demonstrated in wild-type strain N2. The 1 µg/mL dose was the most effective, either alone or added to a food matrix, and also significantly decreased triglyceride content in nematodes fed on the CLA mixture. Furthermore, the antiobesity effect was related to the CLA isomer trans-10, cis-12. Finally, the transcriptional study showed C. elegans fed with Tonalin (1 µg/mL) underwent an upregulation of energy metabolism, reproduction, protein metabolism and oxidative stress processes. In conclusion, the results presented here clearly correlate well with other animal studies, demonstrating the value of C. elegans as a useful model to evaluate antiobesity compounds/ingredients.

Dietary linoleate preserves cardiolipin and attenuates mitochondrial dysfunction in the failing rat heart.

AIMS: Cardiolipin (CL) is a tetra-acyl phospholipid that provides structural and functional support to several proteins in the inner mitochondrial membrane. The majority of CL in the healthy mammalian heart contains four linoleic acid acyl chains (L(4)CL). A selective loss of L(4)CL is associated with mitochondrial dysfunction and heart failure in humans and animal models. We examined whether supplementing the diet with linoleic acid would preserve cardiac L(4)CL and attenuate mitochondrial dysfunction and contractile failure in rats with hypertensive heart failure. METHODS AND RESULTS: Male spontaneously hypertensive heart failure rats (21 months of age) were administered diets supplemented with high-linoleate safflower oil (HLSO) or lard (10% w/w; 28% kilocalorie fat) or without supplemental fat (control) for 4 weeks. HLSO preserved L(4)CL and total CL to 90% of non-failing levels (vs. 61-75% in control and lard groups), and attenuated 17-22% decreases in state 3 mitochondrial respiration observed in the control and lard groups (P < 0.05). Left ventricular fractional shortening was significantly higher in HLSO vs. control (33 ± 2 vs. 29 ± 2%, P < 0.05), while plasma insulin levels were lower (5.4 ± 1.1 vs. 9.1 ± 2.3 ng/mL; P < 0.05), with no significant effect of lard supplementation. HLSO also increased serum concentrations of several eicosanoid species compared with control and lard diets, but had no effect on plasma glucose or blood pressure. CONCLUSION: Moderate consumption of HLSO preserves CL and mitochondrial function in the failing heart and may be a useful adjuvant therapy for this condition.

Funcionalidad y recomendaciones nutricionales de ácidos grasos esenciales y sus derivados en la alimentación del lactante a partir de los 6 meses de edad / Functonality and nutritional recommendations of essential fatty acids and their derivatives in breastfeeders of six months onwards

Los requerimientos de ácidos grasos esenciales (AGEs) y ácidos grasos poliinsaturados de cadena larga (AGPI-CL) durante los últimos meses de gestación y los primeros años de vida son importantes de acuerdo al crecimiento y desarrollo neuronal que está teniendo lugar durante este periodo de vida. El objetivo de este trabajo ha sido destacar la importancia de garantizar un correcta ingesta de AGEs para cubrir los requerimientos nutricionales de estos, a través de la ingesta de alimentos que contienen en su composición nutricional a estos ácidos de forma natural o han sido enriquecidos con ellos. La metodología empleada para este fin ha sido la utilización de bases de datos electrónicas como MedLine, ScienceDirect, Scirus, Trip database y de la hemeroteca científica de la Universidad de Murcia; También han sido consultadas las páginas web de organismos nacionales e internacionales tales como la Asociación Española de Pediatría (AEP), Agencia Europea de Seguridad Alimentaria (EFSA) y European Society of Pediatric, Gastroenterology, Health and Nutrition (ESPGHAN). Los resultados obtenidos muestran como los AGEs e incluso los AGPI-CL (DHA y ARA) son esenciales para el correcto desarrollo del lactante y niño de corta edad; pues aún estando el lactante desde el primer día de vida dotado de todo el sistema enzimático necesario para la conversión de AGEs en sus correspondientes AGPI-CL y sus derivados, esta conversión podría ser insuficiente, siendo necesario y/o esencial el aporte de estos AGPI-CL a través de la dieta. Las conclusiones derivadas de este trabajo fueron que durante los seis primeros meses de vida el aporte de AGEs y AGPI-CL está asegurado a través de la leche materna o en su defecto a través de las fórmulas de inicio; a partir de los 6 meses con la introducción de la alimentación complementaria y la introducción de la leche de vaca a partir de los 12 meses de vida (introducción en contra de las recomendaciones de ESPGHAN), podría verse comprometida la aportación de estos ácidos. Existe un vacío legal en cuanto a la aportación de AGEs a través de la alimentación complementaria distinta a los cereales; sin embargo, comités como el de la AEP recomienda que en los tarritos infantiles de carnes y pescados con verdura, el aporte de AL sea entre 3-4.5% de la energía de la dieta y al menos 0.5% desde ALN para satisfacer los requerimientos de AGEs en lactantes y niños de corta edad (AU)

Essential fatty acids and long-chain unsaturated fatty acids are important for growth and neuronal development during the final months of gestation and the early years of life. The aim of this study is to highlight the importance of ensuring a correct intake of EFAs for nutritional requirements through the intake of foods which naturally contain these acids or which have been enriched with them. The methodology used was basee on the review of electronic databases MedLine, ScienceDirect, Scirus, Trip database and that of the scientific journal library of the University of Murcia. National and international websites such as the Asociación Española de Pediatría (AEP), European Agency for Food Safety (EAFS) and the European Society of Pediatric, Gastroenterology, Health and Nutrition (ESPGHAN) were also consulted. The results show how EFAs and also AGPI-CL (DHA and ARA) are essential for the correct development of breastfeeders and infants. Even though the breastfeeder is enzymatically fully equipped from the first day of life to convert EFAs into AGPI-CL and derivatives, the conversion may be insufficient and it may be necessary to include AGPI-CL in the diet. The conclusions are that during the first 6 months of life the provision of EFAs and AGPI-CL is assured thanks to the mother’s milk or through starter formulas; at six months the introduction of complementary foods and the adaptation to cow’s milk at twelve months (against the recommendations of the ESPGHAN) may affect the provision of these acids. There is a legal vacuum in the issue of the provision of EFAs through complementary foods other than cereals although committees like the AEP recommend that AL in meat and fish baby foods with vegetables should suppose 3-4.5% of the energy provision, and ALN at least 0.5% in order to satisfy EFA requirements in breastfee ans infants (AU)

Dietary modulation of body composition and insulin sensitivity during catch-up growth in rats: effects of oils rich in n-6 or n-3 PUFA.

The present study investigates whether excessive fat accumulation and hyperinsulinaemia during catch-up growth on high-fat diets are altered by n-6 and n-3 PUFA derived from oils rich in either linoleic acid (LA), α-linolenic acid (ALA), arachidonic acid (AA) or DHA. It has been shown that, compared with food-restricted rats refed a high-fat (lard) diet low in PUFA, those refed isoenergetically on diets enriched in LA or ALA, independently of the n-6:n-3 ratio, show improved insulin sensitivity, lower fat mass and higher lean mass, the magnitude of which is related to the proportion of total PUFA precursors (LA+ALA) consumed. These relationships are best fitted by quadratic regression models (r2>0·8, P < 0·001), with threshold values for an impact on body composition corresponding to PUFA precursors contributing 25-30 % of energy intake. Isoenergetic refeeding on high-fat diets enriched in AA or DHA also led to improved body composition, with increases in lean mass as predicted by the quadratic model for PUFA precursors, but decreases in fat mass, which are disproportionately greater than predicted values; insulin sensitivity, however, was not improved. These findings pertaining to the impact of dietary intake of PUFA precursors (LA and ALA) and their elongated-desaturated products (AA and DHA), on body composition and insulin sensitivity, provide important insights into the search for diets aimed at counteracting the pathophysiological consequences of catch-up growth. In particular, diets enriched in essential fatty acids (LA and/or ALA) markedly improve insulin sensitivity and composition of weight regained, independently of the n-6:n-3 fatty acid ratio.

Modulatory effect of fatty acids on fungicidal activity, respiratory burstand TNF-a and IL-6 production in J774 murine macrophages

The reported effects of different families of fatty acids (FA; SFA, MUFA, n-3 and n-6 PUFA) on human health and the importance of macrophagerespiratory burst and cytokine release to immune defence led us to examine the influence of palmitic acid (PA), oleic acid (OA),linoleic acid, arachidonic acid, EPA and DHA on macrophage function. We determined fungicidal activity, reactive oxygen species(ROS) and cytokine production after the treatment of J774 cells with non-toxic concentrations of the FA. PA had a late and discrete stimulatingeffect on ROS production, which may be associated with the reduced fungicidal activity of the cells after treatment with this FA.OA presented a sustained stimulatory effect on ROS production and increased fungicidal activity of the cells, suggesting that enrichmentof diets with OA may be beneficial for pathogen elimination. The effects of PUFA on ROS production were time- and dose-dependentlyregulated, with no evident differences between n-3 and n-6 PUFA. It was worth noting that most changes induced after stimulation of thecells with lipopolysaccharide were suppressed by the FA. The present results suggest that supplementation of the diet with specific FA, notclasses of FA, might enable an improvement in host defence mechanisms or a reduction in adverse immunological reactions.