RESUMEN
BACKGROUND: Allergen information on product labels is crucial in food allergy management, though inadequacy in current labelling practices is one of the major causes for accidental reactions upon consuming prepacked food products. OBJECTIVE: This study analyses current status of communicating allergen information on food labels and provides practical recommendations for improving the label format based on communication theory. METHODS: Product labels (N 288) of seven food categories from private label products and brands were obtained at three retailers in the Netherlands. Information regarding the 14 EU-regulated allergens was evaluated by the frequency of emphasizing allergens in the ingredient list, use of precautionary allergen labelling (PAL), icons and an allergen information section. Effectiveness of communication was assessed evaluating readability and findability of information on allergens using principles of Gestalt and Cognitive Load theories. RESULTS: As requested by EU regulation 1169/2011, emphasizing allergens in the ingredient list was almost 100%, all other presentations of information on allergens on labels was highly diverse. A separate allergen information section was present on most private label products. This section could, but not necessarily did, repeat allergens from the ingredient list and/or give a PAL. Brands often provided a PAL at the end of the ingredient list. Part of the products displayed an icon at different locations of the label. Label background, a lack of cohesion and variation in location of topics hamper the identification of relevant information on allergens by (allergic) consumers. Recommendations include a standardized order for mandatory and voluntary topics on the label and a separate allergen information section. CONCLUSION AND CLINICAL RELEVANCE: Overall, consumers encounter a wide and inconsistent range in ways of presentation of allergen information on labels. Standardization according to basic design principles can improve usability and support safe food purchases for allergic consumers.
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Alérgenos , Comunicación , Hipersensibilidad a los Alimentos/terapia , Etiquetado de Alimentos , Países BajosRESUMEN
BACKGROUND: Understanding consumers' interpretation of allergy information is crucial for effective food safety policies. We evaluated consumer understanding of allergy information on foods in controlled, experimental studies. METHOD: Using 18 packaged foods, we evaluated consumer understanding of information about allergens in two experiments: First, a comparison of foods with no stated allergen versus allergen as a stated ingredient versus a precautionary allergen label (PAL); second, a comparison of three common variants of PAL. In each experiment, consumers with and without self-reported food allergy were asked to estimate the risk of allergic reaction and to rate the comprehensibility of the allergen information. In the second experiment, consumers were also asked which form of PAL they preferred. RESULTS: Risk of reaction was assessed as high and low for foods with the allergen stated as ingredient, or without any mention of allergen. However, risk assessment for PAL varied and was judged as higher by non-allergic than allergic participants (82% vs. 58%, p < .001). Understanding of risk associated with PAL also varied by health literacy (p < .001). Both allergic and non-allergic consumers judged all forms of allergy information to be unclear, especially products with no allergy information for non-allergic consumers. Products with a 'Produced in a Factory' PAL were perceived as less risky than 'May contain' or 'Traces of' PALs (p < .001), less than 40% of participants judged PAL information to be comprehensible, and participants preferred 'May contain' over the other PALs. CONCLUSION: Both allergic and non-allergic consumers find allergen information difficult to interpret on packaged foods and misunderstand PAL, incorrectly distinguishing different risk levels for different PAL wording. Clearer allergy information guidelines are called for, and the use of only one PAL wording is recommended.
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Alérgenos , Hipersensibilidad a los Alimentos , Alimentos , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/etiología , Etiquetado de Alimentos , Inocuidad de los Alimentos , HumanosRESUMEN
The origin of N-acyl ethanolamides (NAEs) in plasma is not well understood, and it is possible that NAEs are present in plasma in esterified form. To test this hypothesis, a new and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of arachidonoyl ethanolamide, 2-arachidonoyl glycerol, docosahexaenoyl ethanolamide, dihomo-γ-linolenoyl ethanolamide, oleoyl ethanolamide, palmitoyl ethanolamide, and stearoyl ethanolamide in 100 µl of human plasma using a simple acetonitrile extraction step. Using this method, we determined (i) free and esterified NAE levels in human plasma, (ii) free and esterified NAE levels in plasma of mice fed with diets with different amounts of n-3 fatty acids, and (iii) esterified NAE levels in blood cells. Murine and human plasma extracts contained 20- to 60-fold higher levels of esterified NAEs than free NAEs. Moreover, the effect of dietary n-3 fatty acids on murine free plasma NAE profiles was similar for esterified NAEs. Finally, esterified NAEs were also present in murine blood cells, and their pattern followed the same diet effect as observed for free and esterified NAEs in plasma. Together, these data point to the presence of previously ignored pools of esterified NAEs in plasma and blood cells that correlated well with free NAE levels in plasma.
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Células Sanguíneas/química , Análisis Químico de la Sangre/métodos , Cromatografía Liquida , Etanolaminas/sangre , Ácidos Grasos no Esterificados/sangre , Ácidos Grasos/sangre , Espectrometría de Masas en Tándem , Animales , Humanos , Límite de Detección , Ratones , Ratones Endogámicos C57BLAsunto(s)
Alérgenos/inmunología , Hiperreactividad Bronquial/inmunología , Hipersensibilidad a los Alimentos/inmunología , Tenebrio/inmunología , Animales , Hiperreactividad Bronquial/diagnóstico , Hipersensibilidad a los Alimentos/diagnóstico , Humanos , Inmunización , Inmunoglobulina E/inmunología , Inmunoglobulina G/farmacología , Pruebas CutáneasRESUMEN
Following the discovery of the endocannabinoid arachidonoyl ethanolamide (anandamide) and other N-acyl-ethanolamines, several other compounds have been found in which amino acids or neurotransmitters rather than ethanolamide are linked to fatty acids. Studies have shown that the local availability of fatty acid precursors, which in turn is modulated by dietary intake of lipids, determines the pattern of conjugates formed. Less information is available whether the same might be true for the amines or neurotransmitters involved. We hypothesized that N-arachidonoyl-serotonin (AA-5-HT) and its analogs could be endogenously present in those tissues that have high contents of serotonin. We investigated the endogenous presence of N-acyl serotonins in different parts of the gastro-intestinal tract of pigs and mice. We discovered that AA-5-HT, oleoyl-serotonin, palmitoyl-serotonin, and stearoyl-serotonin were endogenously present, particularly in the jejunum and ileum. Their formation in vitro was stimulated by the addition of serotonin to intestinal tissue incubations. Furthermore, in a mouse study we showed that the pattern of formation is dependent on the relative amount of fatty acids in the diet. The formation of docosahexaenoyl-serotonin and eicosapentaenoyl-serotonin was elevated in mice fed with a diet containing fish oil. Preliminary data showed that several of the serotonin conjugates are able to inhibit glucagon-like peptide-1 secretion and FAAH activity in vitro. Taken together, our data suggest that N-acyl serotonins are a novel class of lipid mediators present in the gut with highly promising biological properties.
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Ácidos Grasos/metabolismo , Mucosa Intestinal/metabolismo , Serotonina/química , Serotonina/metabolismo , Animales , Masculino , Ratones , Serotonina/análogos & derivados , Porcinos , Espectrometría de Masas en TándemRESUMEN
n-3 PUFAs have beneficial health effects which are believed to be partly related to their anti-inflammatory properties, however the exact mechanisms behind this are unknown. One possible explanation could be via their conversion to N-acyl ethanolamines (NAEs), which are known to possess anti-inflammatory properties. Using fatty acid precursors we showed that 3T3-L1 adipocytes are indeed able to convert docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to their NAE derivatives docosahexaenoyl ethanolamine (DHEA) and eicosapentaenoyl ethanolamine (EPEA), respectively. This synthesis took place on top of an apparent background formation of these NAEs in standard culture medium. In addition we were able to demonstrate the presence of DHEA, but not of EPEA, in human plasma. DHEA and EPEA were found to decrease LPS induced adipocyte IL-6 and MCP-1 levels. Results of combined incubations with PPAR-gamma and CB2 antagonists suggest a role of these receptors in mediating the reduction of IL-6 by DHEA. Our results are in line with the hypothesis that in addition to other pathways, formation of N-acyl ethanolamines may contribute to the biological activity of n-3 PUFAs. Different targets, including the endocannabinoid system, may be involved in the immune-modulating activity of these "fish-oil-derived NAEs."
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Adipocitos/metabolismo , Antiinflamatorios/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Etanolaminas/metabolismo , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Animales , Quimiocina CCL2/metabolismo , Medios de Cultivo , Ácidos Docosahexaenoicos/sangre , Ácidos Docosahexaenoicos/química , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/sangre , Ácido Eicosapentaenoico/química , Ácido Eicosapentaenoico/farmacología , Etanolaminas/química , Humanos , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Espectrometría de Masas , RatonesRESUMEN
To contribute to the hazard identification of low molecular weight (LMW) respiratory allergens, respiratory allergy induced by trimellitic anhydride (TMA) was characterized by whole genome analysis of lung tissue and blood proteomics in Brown Norway rats. Dermal sensitization (50% and 25% w/v) with TMA and an inhalation challenge of 15 mg/m(3) TMA-induced apneas, laryngeal inflammation, increased numbers of eosinophils, neutrophils and macrophages in bronchoalveolar lavage (BAL), and increased immunoglobulin E levels in serum and lung tissue. Whole genome analysis of lung, sampled 24 hours after challenge, showed expression changes of not only genes belonging to several Gene Ontology groups with up-regulation of inflammatory-associated genes and those associated with lung remodeling but also genes involved in downsizing these processes. Blood proteomics reflected activation of inflammation-inhibiting pathways. Unsensitized animals challenged with TMA exhibited also an increased number of macrophages in BAL, but gene expression in the above-mentioned gene pathways was unchanged or down-regulated. The authors conclude that parameters for lung remodeling can be a valuable tool in hazard identification of LMW respiratory allergens.
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Alérgenos/toxicidad , Anhídridos Ftálicos/toxicidad , Hipersensibilidad Respiratoria/genética , Hipersensibilidad Respiratoria/metabolismo , Alérgenos/administración & dosificación , Análisis de Varianza , Animales , Lavado Broncoalveolar , Análisis por Conglomerados , Femenino , Perfilación de la Expresión Génica , Inmunoglobulina E/metabolismo , Inmunohistoquímica , Pulmón/metabolismo , Pulmón/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Anhídridos Ftálicos/administración & dosificación , Análisis de Componente Principal , Proteómica , Ratas , Ratas Endogámicas BN , Hipersensibilidad Respiratoria/sangre , Transducción de Señal/efectos de los fármacos , Estadísticas no Paramétricas , Receptores Toll-Like/metabolismoRESUMEN
SCOPE: The growing world population is a key driver for the exploration of sustainable protein sources to ensure food security. Mealworm and other insects are promising candidates. Previously we found that shrimp allergic patients are at risk for mealworm allergy, and that mealworm can induce a primary allergy . This study set out to investigate the allergenic potential of edible insects, suggested for human consumption by agencies such as WHO/FAO, in both the shrimp (potentially cross-reactive) and primary mealworm allergic population. The following insects were studied: mealworm, house cricket, giant mealworm, lesser mealworm, African grasshopper, large wax moth, and black soldier fly. METHODS AND RESULTS: Fifteen shrimp (mealworm sensitized or allergic) patients and four primary mealworm allergic subjects, who participated in previous studies, were included. All shrimp allergic patients were sensitized to multiple insects with similar response profiles for all insects tested. Primary mealworm allergic patients, showed IgE binding to proteins from only a few insects on immunoblot, although basophil activation test was positive for all tested insects. CONCLUSION: Shrimp allergic patients are most likely at risk of food allergy to mealworm and other insects. Primary mealworm allergy does not mean subjects are likely to react to all insects.
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Hipersensibilidad a los Alimentos/inmunología , Penaeidae/inmunología , Tenebrio/inmunología , Adulto , Anciano , Animales , Reacciones Cruzadas , Femenino , Humanos , Inmunoglobulina E/inmunología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP). MAIN BODY: The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell-cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential. CONCLUSION: The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.org platform to expand the mechanistic data, improve the confidence in each of the proposed KE and key event relations (KERs), and allow for the identification of new, or refinement of established KE and KERs.
RESUMEN
Vascular endothelial growth factor (VEGF), oncostatin M (OSM), and granulocyte chemotactic protein-2 (GCP-2/CXCL6) are up-regulated in U937 macrophages and peripheral blood macrophages exposed to LPS, beta-adrenergic receptor (beta2-AR) agonists (e.g. zilpaterol, and clenbuterol) and some other agents that induce intracellular cAMP (prostaglandin E2, forskolin, and butyryl cAMP). LPS in combination with beta2-agonists and cAMP elevating agents had an additional effect on the release of VEGF, OSM, and CXCL6. These proteins are up-regulated after 16-24 h of exposure and this is mediated by the beta2-AR, as determined by time course experiments and the use of a specific beta2-AR antagonist (ICI 118551). Beta2-AR agonists are used as bronchodilators in the treatment of asthma, but appear to have no effect on the chronic inflammation of the disease. However, the up-regulation of VEGF, OSM, and CXCL6 may have adverse effects on the inflammatory process of asthma. These mediators are involved in the recruitment of neutrophils, airway remodelling and angiogenesis, known features of chronic inflammatory diseases. We propose that the up-regulation of these proteins could play a role in the adverse effects of prolonged excessive usage of beta2-AR agonists on the airways besides the desensitization of the beta2-AR.
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Agonistas Adrenérgicos beta/farmacología , Quimiocinas CXC/biosíntesis , Citocinas/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Bucladesina/farmacología , Quimiocina CXCL6 , Clenbuterol/farmacología , Colforsina/farmacología , AMP Cíclico/biosíntesis , Dinoprostona/farmacología , Humanos , Lipopolisacáridos/farmacología , Activación de Macrófagos/efectos de los fármacos , Oncostatina M , Compuestos de Trimetilsililo/farmacología , Células U937 , Regulación hacia Arriba/efectos de los fármacosRESUMEN
There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Delta(9)-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa extracts and its main non-psychoactive constituent Delta(9)-tetrahydrocanabinoid acid (THCa). By heating Cannabis extracts, THCa was shown to be converted into THC. Unheated Cannabis extract and THCa were able to inhibit the tumor necrosis factor alpha (TNF-alpha) levels in culture supernatants from U937 macrophages and peripheral blood macrophages after stimulation with LPS in a dose-dependent manner. This inhibition persisted over a longer period of time, whereas after prolonged exposure time THC and heated Cannabis extract tend to induce the TNF-alpha level. Furthermore we demonstrated that THCa and THC show distinct effects on phosphatidylcholine specific phospholipase C (PC-PLC) activity. Unheated Cannabis extract and THCa inhibit the PC-PLC activity in a dose-dependent manner, while THC induced PC-PLC activity at high concentrations. These results suggest that THCa and THC exert their immuno-modulating effects via different metabolic pathways.
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Cannabis/química , Cannabis/inmunología , Dronabinol/farmacología , Factores Inmunológicos , Receptor Cannabinoide CB1/efectos de los fármacos , Receptor Cannabinoide CB2/efectos de los fármacos , Línea Celular , Células Cultivadas , AMP Cíclico/farmacología , Relación Dosis-Respuesta a Droga , Calor , Humanos , Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Receptor Cannabinoide CB1/antagonistas & inhibidores , Receptor Cannabinoide CB2/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Fosfolipasas de Tipo C/metabolismoRESUMEN
Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed. In this review the impact of processing (heat and non-heat treatment) on the allergenic potential of proteins, and on the antigenic (IgG-binding) and allergenic (IgE-binding) properties of proteins has been considered. A variety of allergenic foods (peanuts, tree nuts, cows' milk, hens' eggs, soy, wheat and mustard) have been reviewed. The overall conclusion drawn is that processing does not completely abolish the allergenic potential of allergens. Currently, only fermentation and hydrolysis may have potential to reduce allergenicity to such an extent that symptoms will not be elicited, while other methods might be promising but need more data. Literature on the effect of processing on allergenic potential and the ability to induce sensitisation is scarce. This is an important issue since processing may impact on the ability of proteins to cause the acquisition of allergic sensitisation, and the subject should be a focus of future research. Also, there remains a need to develop robust and integrated methods for the risk assessment of food allergenicity.
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Alérgenos/química , Manipulación de Alimentos/métodos , Hipersensibilidad a los Alimentos , Calor , Proteínas/inmunología , Humanos , Proteínas/químicaRESUMEN
The discovery of new anti-inflammatory drugs is often based on an interaction with a specific target, although other pathways often play a primary or secondary role. Anti-inflammatory drugs can be categorized into classes, based on their mechanism of action. In this article we investigate the possibility to characterize novel anti-inflammatory compounds by three holistic methods. For this purpose, we make use of macrophage-like U937 cells which are stimulated with LPS in the absence or presence of an anti-inflammatory compound. Using micro-arrays, 2-D gel electrophoresis and a LC-MS method for lipids the effects on the transcriptome, proteome and metabolome of the exposed cells is investigated. The expression patterns are subsequently analyzed using in-house developed pattern recognition tools. Using the methods described above, we have examined the effects of six anti-inflammatory compounds. Our results demonstrate that different classes of anti-inflammatory compounds show distinct and characteristic mRNA, protein, and lipid expression patterns, which can be used to categorise known molecules and to discover and classify new leads. The potential of our approach is illustrated by the analysis of several beta (2)-adrenergic agonists (beta2-agonists). In addition to their primary pharmacological target, beta2-agonists posses certain anti-inflammatory properties. We were able to show that zilpaterol, a poorly characterized beta2-agonist, gives rise to an almost identical expression pattern as the beta2-agonists clenbuterol and salbutamol. Furthermore we have identified specific mRNA, protein and lipid markers for the anti-inflammatory compounds investigated in this study.
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Antiinflamatorios/farmacología , Lípidos/biosíntesis , Macrófagos , Proteoma/biosíntesis , ARN Mensajero/biosíntesis , Agonistas de Receptores Adrenérgicos beta 2 , Agonistas Adrenérgicos beta/farmacología , Línea Celular Tumoral , Electroforesis en Gel Bidimensional , Cromatografía de Gases y Espectrometría de Masas , Humanos , Lipopolisacáridos/farmacología , Activación de Macrófagos/efectos de los fármacos , Activación de Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Análisis Multivariante , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
In view of the imminent deficiency of protein sources for human consumption in the near future, new protein sources need to be identified. However, safety issues such as the risk of allergenicity are often a bottleneck, due to the absence of predictive, validated and accepted methods for risk assessment. The current strategy to assess the allergenic potential of proteins focuses mainly on homology, stability and cross-reactivity, although other factors such as intestinal transport might be of added value too. In this review, we present an overview of the knowledge of protein transport across the intestinal wall and the methods currently being used to measure this. A literature study reveals that protein transport in sensitised persons occurs para-cellularly with the involvement of mast cells, and trans-cellularly via enterocytes, while in non-sensitised persons micro-fold cells and enterocytes are considered most important. However, there is a lack of comparable systematic studies on transport of allergenic proteins. Knowledge of the multiple protein transport pathways and which model system can be useful to study these processes may be of added value in the risk assessment of food allergenicity.
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Alérgenos/metabolismo , Hipersensibilidad a los Alimentos/metabolismo , Intestino Delgado/metabolismo , Transporte de Proteínas , Animales , Proteínas en la Dieta/inmunología , Proteínas en la Dieta/metabolismo , Enterocitos/metabolismo , Humanos , Intestino Delgado/inmunología , Mastocitos/metabolismoRESUMEN
SCOPE: Due to the imminent growth of the world population, shortage of protein sources for human consumption will arise in the near future. Alternative and sustainable protein sources (e.g. insects) are being explored for the production of food and feed. In this project, the safety of Yellow mealworms (Tenebrio molitor L.) for human consumption was tested using approaches as advised by the European Food Safety Authority for allergenicity risk assessment. METHODS AND RESULTS: Different Yellow mealworm protein fractions were prepared, characterised, and tested for cross-reactivity using sera from patients with an inhalation or food allergy to biologically related species (House dust mite (HDM) and crustaceans) by immunoblotting and basophil activation. Furthermore, the stability was investigated using an in vitro pepsin digestion test. IgE from HDM- and crustacean allergic patients cross-reacted with Yellow mealworm proteins. This cross-reactivity was functional, as shown by the induction of basophil activation. The major cross-reactive proteins were identified as tropomyosin and arginine kinase, which are well known allergens in arthropods. These proteins were moderately stable in the pepsin stability test. CONCLUSION: Based on these cross-reactivity studies, there is a realistic possibility that HDM- and crustacean allergic patients may react to food containing Yellow mealworm proteins.
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Reacciones Cruzadas , Crustáceos/inmunología , Aditivos Alimentarios , Hipersensibilidad/inmunología , Proteínas de Insectos/inmunología , Ácaros/inmunología , Tenebrio/inmunología , Animales , HumanosRESUMEN
Palmitoylethanolamide (PEA) belongs to the N-acyl ethanolamines (NAEs), a group of endogenous compounds involved in a variety of physiological processes, including energy homeostasis and inflammation. This review focuses on the analysis of PEA in plasma and tissues and discusses effects of diet and some pathological processes on PEA levels. Originally isolated from egg yolk, PEA has been detected in a variety of tissues and plasma of different species. The compound is present at relatively high levels compared to other NAEs and now mostly analysed using liquid chromatography coupled to mass spectrometry. PEA plasma concentrations show marked fluctuations during the day. However, concentrations in tissues are likely to be more relevant than those in plasma. Most studies suggest that compared to other NAEs, tissue PEA tissue levels are not influenced by changes in dietary fatty acid composition. Effects of inflammation and disease on PEA tissue levels show differences between different models and studies. Therefore, more research is needed on the endogenous role and tissue kinetics of PEA during disease. The rediscovery of the therapeutic potential of PEA has fuelled research and the development of new pharmaceutical formulations. With regard to this there is a need for better kinetic data and models, preferably also on its tissue disposition. Moreover, it is important to learn more about effects of exogenous PEA on the kinetics of other NAEs (and endocannabinoids) and effects of inhibiting its breakdown using inhibitors of the degrading enzymes fatty acid amide hydrolase or N-acylethanolamine-hydrolyzing acid amidase.
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Endocannabinoides/química , Endocannabinoides/metabolismo , Etanolaminas/química , Etanolaminas/metabolismo , Ácidos Palmíticos/química , Ácidos Palmíticos/metabolismo , Amidas , Animales , Cromatografía Liquida/métodos , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/efectos adversos , Metabolismo Energético/fisiología , Ácidos Grasos/efectos adversos , Ácidos Grasos/fisiología , Humanos , Inflamación/metabolismo , Inflamación/patología , Espectrometría de Masas/métodos , Distribución Tisular/fisiologíaRESUMEN
It is well established that dietary intake of n-3 fatty acids is associated with anti-inflammatory effects, and this has been linked to modulation of the oxylipin and endocannabinoid metabolomes. However, the amount of data on specific tissue effects is limited, and it is not known how inflammation affects this relation. In the present study we systematically explored the combined effects of n-3 fatty acid diets and inflammation on the in vivo endocannabinoid and oxylipin metabolomes using a multicompartment, detailed targeted lipidomics approach. Male C57BL/6 mice received diets containing 0, 1, or 3 % w/w fish oil (FO) for 6 weeks, after which 2 mg/kg LPS or saline was administered i.p. Levels of endocannabinoids/N-acylethanolamines (NAEs) and oxylipins, covering n-3 and n-6 fatty acid derived compounds, were determined in plasma, liver, ileum and adipose tissue using LC-MS/MS. FO generally increased 'n-3' NAEs and oxylipins at the expense of compounds derived from other fatty acids, affecting all branches of the oxylipin metabolome. LPS generally increased levels of endocannabinoids/NAEs and oxylipins, with opposing effects across plasma and tissues. Multivariate data analysis revealed that separation between diet groups in the saline treated groups was primarily explained by decreases in other than n-3 derived compounds. In the LPS treated groups, the separation was primarily explained by increases in n-3 derived compounds. In conclusion, FO caused marked changes in the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes, with specific effects depending on inflammatory status. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-012-0421-9) contains supplementary material, which is available to authorized users.
RESUMEN
Eicosanoids and endocannabinoids/N-acylethanolamines (NAEs) are fatty acid derived compounds with a regulatory role in inflammation. Considering their complex metabolism, it is likely that inflammation affects multiple compounds at the same time, but how lipid profiles change in plasma and other tissues after an inflammatory stimulus has not been described in detail. In addition, dietary fish oil increases levels of several n-3 fatty acid derived eicosanoids and endocannabinoids, and this may lead to a broader change in the profiles of bioactive lipids. In the present study mice were fed a diet containing 3% w/w fish oil for 6 weeks before receiving i.p. saline or 3 mg/kg lipopolysaccharide (LPS) to induce an inflammatory response. Eicosanoid and endocannabinoid/NAE levels (in total 61 metabolites) in plasma, liver, ileum, and adipose tissue were quantified using targeted lipidomics after 2, 4, 8, and 24 h, respectively. Tissue- and time-dependent effects of LPS on bioactive lipid profiles were observed. For example, levels of CYP derived eicosanoids in the ileum were markedly affected by LPS, whereas this was less pronounced in the plasma and adipose tissue. For some compounds, such as 9,10-DiHOME, opposing effects of LPS were seen in the plasma compared to the other tissues, suggesting differential regulation of bioactive lipid levels after an inflammatory stimulus. Taken together, our results show that plasma levels do not always correlate with the effects found in the tissues, which underlines the need to measure profiles and pathways of mediators involved in inflammation, including endocannabinoid-like structures, in both plasma and tissues.
Asunto(s)
Moduladores de Receptores de Cannabinoides/metabolismo , Grasas Insaturadas en la Dieta/administración & dosificación , Eicosanoides/metabolismo , Endocannabinoides , Aceites de Pescado/administración & dosificación , Inflamación/dietoterapia , Inflamación/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Moduladores de Receptores de Cannabinoides/sangre , Eicosanoides/sangre , Íleon/efectos de los fármacos , Íleon/metabolismo , Inflamación/sangre , Inflamación/inducido químicamente , Lipopolisacáridos/toxicidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Redes y Vías Metabólicas , Ratones , Ratones Endogámicos C57BL , Factores de TiempoRESUMEN
BACKGROUND: n-3 polyunsaturated fatty acids, namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), reduce the risk of cardiovascular disease and can ameliorate many of obesity-associated disorders. We hypothesised that the latter effect will be more pronounced when DHA/EPA is supplemented as phospholipids rather than as triglycerides. METHODOLOGY/PRINCIPAL FINDINGS: In a 'prevention study', C57BL/6J mice were fed for 9 weeks on either a corn oil-based high-fat obesogenic diet (cHF; lipids â¼35% wt/wt), or cHF-based diets in which corn oil was partially replaced by DHA/EPA, admixed either as phospholipids or triglycerides from marine fish. The reversal of obesity was studied in mice subjected to the preceding cHF-feeding for 4 months. DHA/EPA administered as phospholipids prevented glucose intolerance and tended to reduce obesity better than triglycerides. Lipemia and hepatosteatosis were suppressed more in response to dietary phospholipids, in correlation with better bioavailability of DHA and EPA, and a higher DHA accumulation in the liver, white adipose tissue (WAT), and muscle phospholipids. In dietary obese mice, both DHA/EPA concentrates prevented a further weight gain, reduced plasma lipid levels to a similar extent, and tended to improve glucose tolerance. Importantly, only the phospholipid form reduced plasma insulin and adipocyte hypertrophy, while being more effective in reducing hepatic steatosis and low-grade inflammation of WAT. These beneficial effects were correlated with changes of endocannabinoid metabolome in WAT, where phospholipids reduced 2-arachidonoylglycerol, and were more effective in increasing anti-inflammatory lipids such as N-docosahexaenoylethanolamine. CONCLUSIONS/SIGNIFICANCE: Compared with triglycerides, dietary DHA/EPA administered as phospholipids are superior in preserving a healthy metabolic profile under obesogenic conditions, possibly reflecting better bioavalability and improved modulation of the endocannabinoid system activity in WAT.
Asunto(s)
Moduladores de Receptores de Cannabinoides/metabolismo , Dieta Alta en Grasa , Endocannabinoides , Ácidos Grasos Omega-3/metabolismo , Obesidad/dietoterapia , Fosfolípidos/metabolismo , Tejido Adiposo Blanco/metabolismo , Análisis de Varianza , Animales , Disponibilidad Biológica , Peso Corporal , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/farmacología , Inmunohistoquímica , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Metabolómica , Ratones , Ratones Endogámicos C57BL , Microscopía , Músculo Esquelético/metabolismo , Obesidad/prevención & control , Reacción en Cadena en Tiempo Real de la Polimerasa , Triglicéridos/metabolismoRESUMEN
Bisphenol A diglycidyl ether (BADGE) is an epoxide that is used as a starting substance in the manufacture of can coatings for food-contact applications. Following migration from the can coating into food, BADGE levels decay and new reaction products are formed by reaction with food ingredients. The significant decay of BADGE was demonstrated by liquid chromatographic (LC) analysis of foodstuffs, that is, tuna, apple puree, and beer, spiked with BADGE before processing and storage. Life-science inspired analytical approaches were successfully applied to study the reactions of BADGE with food ingredients, for example, amino acids and sugars. An improved mass balance of BADGE was achieved by selective detection of reaction products of BADGE with low molecular weight food components, using a successful combination of stable isotopes of BADGE and analysis by LC coupled to fluorescence detection (FLD) and high-resolution mass spectrometric (MS) detection. Furthermore, proteomics approaches showed that BADGE also reacts with peptides (from protein digests in model systems) and with proteins in foods. The predominant reaction center for amino acids, peptides, and proteins was cysteine.