Dans les pays industrialisés, les pathologies oculaires à composante vasculaires, que ce soit la rétinopathie du prématuré (ROP), la rétinopathie du diabétique ou la dégénérescence lié à l’âge, représentent la première cause de cécité respectivement chez l’enfant, l’adulte et la personne âgée. Plusieurs études sur l’homme ou sur des modèles animaux ont souligné le rôle crucial joué des acides gras polyinsaturés (AGPI) au cours de ces rétinopathies et notamment l’action préventive des acides gras polyinsaturés oméga 3 (AGPI n-3) sur l’angiogenèse pathologique. Ces AGPI sont estérifiés dans les glycérophospholipides constituant les membranes cellulaires. On les retrouve également dans une classe particulière de glycérophospholipides, les plasmalogènes. La particularité des plasmalogènes réside dans leur liaison vinyl-éther en position sn-1 au lieu d’une liaison ester dans les autres glycérophospholipides. Les AGPI sont libérés des plasmalogènes par une phospholipase indépendante au calcium, la iPLA2, pour devenir des métabolites actifs. Les plasmalogènes via la libération des AGPI joueraient un rôle dans la mise en place et la maturation du réseau vasculaire rétinien et ce, notamment grâce à la bonne mise en place du réseau astrocytaire. Les astrocytes et les cellules de Müller sont les cellules macrogliales qui servent de soutien physique et métabolique à la rétine. De plus, les cellules de Müller participent au métabolisme des lipides. L’objectif de ce travail de thèse a été d’évaluer l’implication des plasmalogènes dans le métabolisme des cellules de Müller et des astrocytes mais aussi dans la communication entre ces cellules macrogliales. Nous avons également étudié le profil lipidique d’enfants prématurés pour mettre en évidence de potentielles altérations du métabolisme des plasmalogènes chez des nouveau-nés développant une rétinopathie à composante vasculaire, la rétinopathie du prématuré (ROP). Pour ce faire nous avons étudié les effets d’une diminution en plasmalogènes et/ou en iPLA2 sur des cellules de Müller en culture primaire après avoir préalablement vérifié l’expression de l’enzyme clef de la biosynthèse des plasmalogènes. Nous avons ensuite étudié les effets d’une diminution des teneurs en plasmalogènes sur la communication calcique entre les cellules de Müller et les astrocytes. Nos résultats ont montré que les cellules de Müller expriment l’enzyme-clé de synthèse des plasmalogènes et que ces cellules sont plus riches en plasmalogènes que la rétine entière. Les plasmalogènes seraient impliqués dans le contrôle de la migration des cellules de Müller par l’action de la voie ERK1/2 MAPK. Ces effets ne semblent pas passer par la libération des AGPI. De plus nos résultats suggèrent une dégradation de la communication entre les astrocytes et les cellules de Müller en cas de diminution des teneurs en plasmalogènes dans les cellules de Müller. Enfin chez l’homme nous avons mis en évidence une accumulation des AGPI n-6 au détriment des AGPI n-3 dans les érythrocytes des enfants développant une rétinopathie du prématuré et inversement dans le groupe d’enfants prématuré contrôle. L’ensemble de ces travaux confirme l’importance du métabolisme lipidique, et plus particulièrement celui des plasmalogènes, sur le fonctionnement de la rétine. / Retinal vascular disorders such as retinopathy of prematurity (ROP), diabetic retinopathy or age-related macular degeneration represent the first cause of vision loss at all ages in industrialized countries. Many epidemiological or animal studies have shown the involvement of polyunsaturated fatty acids (PUFA) in the regulation of vascular development and more specifically the beneficial properties of omega 3 PUFA (n-3 PUFA) against pathological vascularization. Those PUFA are esterified on glycerophospholipids (GP). GP are the primary constituents of the lipid bilayer of cell membranes. PUFA can be also esterified on a specific class of GP, called plasmalogens. Plasmalogens are characterized by the presence of a vinyl ether linkage at the sn-1 position of glycerol instead of an ester linkage as seen in other GP. PUFA are released from plasmalogens by a calcium-independent phospholipase (iPLA2). Free PUFA can be converted into biologically active metabolites. Plasmalogens may have an impact on the development and the maturation of retinal vascular network through the PUFA they release through the control of astrocyte template formation prior to vessel formation. Astrocytes and Müller cells are macroglials cells providing physical and metabolic supports to the retina. Müller cells are key actors of the retinal lipid metabolism. The aim of this work was to evaluate the involvement of plasmalogens in Müller cells and astrocytes metabolism as well as in the ability of these cells to communicate. On one hand, we have studied the effects of a decrease in plasmalogen biosynthesis and/or in iPLA2 activity on Müller cell physiology. Müller cells express a biosynthesis key enzyme of plasmalogen and reducing the biosynthesis of plasmalogens affects Müller cell ability to migrate through the ERK1/2 MAPK signalling. In a second series of studies, we studied the repercussions of such modifications on Müller cell physiology on their ability to communicate with retinal astrocytes through calcium signalling. Our results suggest that affecting plasmalogen metabolism in Müller cells alters the communication between astrocytes and Müller cells. Finally, and in order to investigate whether plasmalogen metabolism may be modified in a human disease displaying abnormal retinal vascular development, we performed a lipidomic study of circulating lipids in infants affected by retinopathy of prematurity. ROP was characterized by the accumulation of n-6 PUFA at the expense of n-3 PUFA, these changes being associated to plasmalogens. All these experiments confirm the importance of lipid metabolism, and especially plasmalogens, on the retina functioning.

The Mediterranean diet (Medi) has been highlighted as the golden diet rich in protective properties associated with cognitive- and emotional health. The foundation of the Medi comprises vegetables, fruits, nuts and seeds, legumes, and extra virgin olive oil. Research has been conducted in both holistic dietary approach and single nutrient approach regarding the impact of nutrition and diet, in this case, the Medi‟s effect on brain health. This review aims to give an up to date overview of the Mediterranean diet, outline some of the diet's abundant nutrients, and discuss studies linking the nutrient's potential effect on depression, cognitive decline, dementia, and brain structure and function. In addition, this review will attempt to assess whether the Medi as a whole or if a single nutrient approach is accountable for the health-promoting findings. Furthermore, the gut-brain axis, and other potential underlying mechanisms involved in the modulation of food- and nutrient intake and their effects on the brain, will be outlined. A diet high in fruit-, vegetable-, polyunsaturated fatty acid-, and monounsaturated fatty acid content has great power for health-maintenance and decreases the risk of suffering cognitive decline, dementia, and potentially depression. More randomized controlled trials are however eagerly awaited to give more substance to previous findings.

This study was a follow-up of the Christiansen study which was completed in 1967. Dr. Christiansen's 26 subjects ranged in age from 33 to 60 years. Ten were designated as controls and the other 16 were placed on a high polyunsaturated fatty acid (PUFA) diet for a period of 26 weeks . The purpose of doing a follow-up was to determine what effect the study had on present dietary patterns, serum lipid levels and rate of erythrocyte hemolysis. Eighteen of the original subjects participated in this study. Of these 18, nine were from the control group and nine were from the experimental group. There were nine women and nine men. The serum cholesterol and triglyceride levels, rate of erythrocyte hemolysis and blood pressure reading were determined. General health status and dietary pattern were determined through the use of a questionnaire. The results of the questionnaire indicate that the experimental diet of the original study had influenced the present diet of the study's subjects. The use of vegetable oils was increased and the consumption of eggs and whole milk was decreased. The study had little effect on the consumption of beef, pork, fish and chicken. The rate of erythrocyte hemolysis was greater for the control group (non-instructed) than for the experimental group (instructed). The mean values were 12. 65 and 9. 49 percent, respectively. The results indicate that there was no depletion of tocopherol levels due to continued use of PUFA. Serum triglyceride levels varied from 60 to 72 mg percent. Mean values for men were slightly higher than for the women. The means for the instructed and non-instructed groups were almost the same (6 7. 2 and 6 7. 0 mg percent, respectively). The cholesterol values ranged from 139 to 252 mg percent. The mean values were close to those at the end of the previous study (192 and 188 mg percent, respectively). There was no correlation between cholesterol values and the rate of erythrocyte hemolysis or triglyceride values.

Biosynthesis of milk conjugated linoleic acid (CLA), a component of milk fat with demonstrated health benefits, requires a dietary source of PUFA. Even with PUFA supplementation, milk CLA is highly variable. Therefore, this study was aimed at identifying factors responsible for the variations in rumen CLA precursors and milk CLA. Study 1 evaluated the efficiency of CLA production by grazing cows compared to those fed grass silage or fresh grass. Grazing cows were more efficient than those fed grass silage or fresh grass in milk CLA production. About 75% of the variability in milk CLA was related to the differences in PUFA (l8:2n-6 + 18:3n-3) intake and the remainder was related to factors regulating the extent of PUFA biohydrogenation in the rumen. This study demonstrated that PUFA intake is important but it is not the only factor responsible for the observed variation in milk CLA production. Study 2 evaluated the effect of diets differing in rate of starch degradation on rumen PUFA biohydrogenation and milk CLA. Concentrations of ruminal t11-18:1 and milk CLA were greater for barley-based diets than corn-based diets and were not different between rolling and grinding, indicating that factors inherent in the source of starch were responsible for the observed differences and these factors could not be modified by rolling or grinding the grain. Study 3 examined the effect of stage of lactation on persistency of milk t10-18:1, t11-18:1 and CLA for control and test (supplemented with PUFA and monensin) diets from calving to 270 days in milk. Milk concentrations of t11-18:1 and RA remained similar across the lactation length and were greater for the test diet compared to the control. Changes in milk t10-18:1 concentration during lactation appeared to reflect an effect of the degree of rumen fermentation on PUFA biohydrogenating bacteria. Although PUFA intake is important for milk CLA production, only those diets that give rise to increased ruminal t11-18:1 result in greater milk CLA. Concentrations of rumen t11-18:1 is influenced by the amount of PUFA consumed, degree of shift to t10-18:1 and the extent of PUFA biohydrogenation in the rumen. / Animal Science

The factors that determine the efficiency of energy transfer in aquatic food webs have been investigated for many decades. The plant-animal interface is the most variable and least predictable of all levels in the food web. In order to study determinants of food quality in a large lake and to test the recently proposed central importance of the long-chained eicosapentaenoic acid (EPA) at the pelagic producer-grazer interface, we tested the importance of polyunsaturated fatty acids (PUFAs) at the pelagic producerconsumer interface by correlating sestonic food parameters with somatic growth rates of a clone of Daphnia galeata. Daphnia growth rates were obtained from standardized laboratory experiments spanning one season with Daphnia feeding on natural seston from Lake Constance, a large pre-alpine lake. Somatic growth rates were fitted to sestonic parameters by using a saturation function. A moderate amount of variation was explained when the model included the elemental parameters carbon (r2 = 0.6) and nitrogen (r2 = 0.71). A tighter fit was obtained when sestonic phosphorus was incorporated (r2 = 0.86). The nonlinear regression with EPA was relatively weak (r2 = 0.77), whereas the highest degree of variance was explained by three C18-PUFAs. The best (r2 = 0.95), and only significant, correlation of Daphnia's growth was found with the C18-PUFA α-linolenic acid (α-LA; C18:3n-3). This correlation was weakest in late August when C:P values increased to 300, suggesting that mineral and PUFA-limitation of Daphnia's growth changed seasonally. Sestonic phosphorus and some PUFAs showed not only tight correlations with growth, but also with sestonic α-LA content. We computed Monte Carlo simulations to test whether the observed effects of α-LA on growth could be accounted for by EPA, phosphorus, or one of the two C18-PUFAs, stearidonic acid (C18:4n-3) and linoleic acid (C18:2n-6). With >99 % probability, the correlation of growth with α-LA could not be explained by any of these parameters. In order to test for EPA limitation of Daphnia's growth, in parallel with experiments on pure seston, growth was determined on seston supplemented with chemostat-grown, P-limited Stephanodiscus hantzschii, which is rich in EPA. Although supplementation increased the EPA content 80-800x, no significant changes in the nonlinear regression of the growth rates with α-LA were found, indicating that growth of Daphnia on pure seston was not EPA limited. This indicates that the two fatty acids, EPA and α-LA, were not mutually substitutable biochemical resources and points to different physiological functions of these two PUFAs. These results support the PUFA-limitation hypothesis for sestonic C:P < 300 but are contrary to the hypothesis of a general importance of EPA, since no evidence for EPA limitation was found. It is suggested that the resource ratios of EPA and α-LA rather than the absolute concentrations determine which of the two resources is limiting growth.

No description available.

Investigating the biosynthesis of long-chain (C20–24) polyunsaturated fatty acids (LC-PUFA), physiologically important compounds including arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in fish is crucial to identify dietary requirements for essential fatty acids (EFA). Moreover, knowledge of the C20–24 LC-PUFA biosynthetic capability of farmed fish species enables us to understand their ability to utilise commonly used raw materials such as vegetable oils, which naturally lack LC-PUFA but include C18 PUFA that are metabolic precursors of LC-PUFA. Studies have shown that the potential of a species for LC-PUFA biosynthesis is associated with the complement and function of fatty acyl desaturase (fads) and elongase of very long chain fatty acid (elovl) genes existing in that species. The present study therefore aimed to investigate these genes in the African catfish (Clarias gariepinus), the most commercially important farmed fish in sub-Saharan Africa. A fads2, a fads6 and four elovl (elovl2, elovl4a, elovl4b, elovl8) cDNAs were cloned and functionally characterised by heterologous expression in yeast. The Fads2 was a bifunctional desaturase enzyme with ∆6∆5 and ∆8 activities, and thus catalysing all the desaturation reactions required for ARA and EPA biosynthesis from C18 precursor fatty acids. Moreover, the C. gariepinus Fads2 enzymes also desaturated 24:5n-3 to 24:6n-3, a ∆6 desaturation required for the biosynthesis of DHA through the so-called “Sprecher pathway”. Functional characterisation of Fads6 by heterologous expression in yeast did not reveal its function. With regards to elongases, the C. gariepinus Elovl2 demonstrated the ability to elongate C20 and C22 PUFA and thus complements the Elovl5 with elongase capability towards C18 and C20 PUFA. The Elovl8 was capable of only limited elongation of C18 and C20 PUFA. Elovl4a and Elovl4b, enable the biosynthesis of very long-chain (>C24) fatty acids, compounds with major roles in vision and fertility of vertebrates. The present study confirmed that C. gariepinus possess all the enzymatic capabilities required for the biosynthesis of ARA, EPA and DHA and, therefore, its physiological EFA requirements could be satisfied with dietary provision of C18 PUFA.

Parmi les œufs de poisson, qui sont une ressource aquatique nutritionnelle intéressante, ceux de la truite arc-en-ciel (Oncorhynchus mykiss) contiennent une quantité élevée de protéines et une huile riche en acides gras polyinsaturés (AGPI), avec une proportion très importante de phospholipides. Cependant, l’œuf de poisson présente une capacité élevée d’auto-protection contre les contraintes extérieures, qui limite la destructuration de son réseau protéique par attaque enzymatique. Ainsi, le degré d’hydrolyse des œufs de la truite l’Alcalase®, la Neutrase® et la Protamex® varie entre 3 et 7 %, ce qui est très faible (20 % dans la majorité des protéines animales). L’extraction des lipides après protéolyse partielle est incomplète, probablement en raison d’interactions fortes avec les protéines faiblement hydrolysées. Ils contiennent une teneur élevée en phospholipides (53 % des lipides totaux) et les acides gras polyinsaturés entrent pour 42 % des acides gras totaux. Les AGPI, notamment le DHA, sont situés préférentiellement en position sn-2 sur la molécule de glycérol ce qui est particulièrement intéressant du point de vue nutritionnel. La stabilité à l’oxydation de l’huile a été étudiée par diverses méthodes, dont la spectrométrie infrarouge à transformée de Fourier. Cette méthode s’est avérée extrêmement intéressante pour une analyse structurale de la dégradation de l’huile en cours d’oxydation. Il peut être conclu que les lipides tirés des œufs de la truite arc-en-ciel ou de poisson en général, ont un réel avenir en matière de complément alimentaire ou nutraceutique, à condition de lever l’obstacle de l’hydrolyse enzymatique des protéines du chorion et du vitellus / Fish eggs, especially those of the rainbow trout (Oncorhynchus mykiss) in the present study, are an interesting nutritional aquatic source. They contain proteins of high value, as well as an oil rich in polyunsaturated fatty acids (PUFA) with a large percentage of phospholipids. However, they exhibit a high auto-protection capacity against environmental constraints and thus, the degree of hydrolysis of rainbow trout eggs by Alcalase®, Neutrase® and Protamex® proteases varied solely within 3-7 %. This value was low compared with the 20 % obtained in most animal proteins. The phospholipid content was high (53 % of total lipids) and PUFA accounted for 42 % of total fatty acids. Among PUFA, DHA was found preferably at the sn-2 position of the glycerol backbone, which is of special interest about nutritional properties. The oil release by enzymatic hydrolysis was found limited compared with chemical methods, probably because of the strong interactions engaged with the incomplete destructured protein network. The oxidative stability of the oil was studied through several methods in which the infrared Fourier transform appeared as the best tool for structural analysis along the oxidation process. As a conclusion, lipids from fish eggs, especially from rainbow trout, could be a nutritional breakthrough, as far the enzymatic hydrolysis of the vitellus and of the chorion proteins is achieved

Le métabolisme énergétique cérébral via l’utilisation du glucose est fortement impliqué dans la production d’énergie nécessaire au fonctionnement du neurone en situation basale et d’activation. Des travaux précédents ont mis en évidence chez le rat chroniquement déficient en acides gras polyinsaturés (AGPI) de la série n-3 une altération de ce métabolisme en situation basale (diminution de l’utilisation cérébrale du glucose et de la densité des transporteurs de glucose GLUT1). Pour cerner les différentes étapes du métabolisme énergétique pouvant être modifiées par les AGPI n-3, l’expression des gènes clés a été mesurée par approche transcriptomique (cartes microfluidiques) chez l’animal déficient en AGPI n-3 ou supplémenté en acide docosahexaénoïque (DHA, 22 :6n-3). Ces mesures ont été réalisées sur deux zones cérébrales (cortex fronto-pariétal et couche CA1 de l’hippocampe) chez les animaux en situation basale et soumis à un environnement enrichi activant ces deux zones cérébrales. Pour ces 2 situations, le niveau d’utilisation cérébrale de glucose a été quantifié par la technique du fluoro-2-déoxyglucose couplée à l’imagerie de tomographie par émissions de positons (18FDG-TEP) chez les animaux déficients en AGPI n-3. L’analyse de la teneur cérébrale en AGPI membranaire a été réalisée par chromatographie en phase gazeuse et une approche in vitro sur culture primaire d’astrocytes a été développée pour apprécier l’impact du DHA sur les paramètres métaboliques de ces cellules.Les principaux résultats montrent que :- la déficience en n-3 diminue de 67% la teneur membranaire en DHA dans les deux zones cérébrales étudiées. Si la déficience induit principalement une diminution spécifique de l’expression de GLUT1 (-33%) dans le cortex fronto-pariétal en situation basale et d’activation, en revanche elle perturbe la neurotransmission glutamatergique dans l’hippocampe en augmentant l’expression des 2 transporteurs de glutamate (GLAST et GLT1). Par ailleurs, les données d’imagerie TEP mettent en évidence un hypométabolisme général du glucose chez les animaux déficients en n-3 en situation basale. Les données recueillies sur le modèle astrocytes soulignent un effet direct du DHA sur l’utilisation du glucose et l’expression de GLUT1 ;- La supplémentation en DHA ne modifie pas de façon appréciable la teneur membranaire en DHA dans les deux zones cérébrales étudiées. Au contraire de la déficience, il apparaît clairement pour la couche CA1 de l’hippocampe que l’expression de l’ensemble des gènes codant pour les complexes enzymatiques du cycle de krebs et de la voie de phosphorylation oxydative est significativement augmentée.Ces résultats originaux laissent ainsi entrevoir la possibilité que les acides gras de cette famille d’AGPI puissent intervenir sur l’énergétique et le fonctionnement de la synapse glutamatergique en modulant 1) le métabolisme glucidique (captage de glucose) et du glutamate en situation de déficit d’apport et 2) la production d’ATP (phosphorylation oxydative) en situation de supplémentation en DHA. L’altération de ces paramètres métaboliques au cours du vieillissement et dans certains désordres neurologiques, liée à un déficit de statut en DHA, mettent en avant les potentialités nutritionnelles des AGPI n-3 comme facteur préventif. / Cerebral energy metabolism via glucose utilization is heavily involved in the production of energy required to the neuron in basal conditions and activation. Previous work has shown in rats chronically deficient in n-3 polyunsaturated fatty acids (PUFA) altered the metabolism in basal condition (decrease of cerebral glucose use and density of glucose transporters GLUT1). To identify the different stages of energy metabolism may be modified by n-3 PUFA, the expression of key genes was measured by transcriptomic approach (Taqman Low Density Arrays) in animals deficient in n-3 PUFA or docosahexaenoic acid supplementation (DHA, 22:6n-3). These measurements were performed on two brain areas (fronto-parietal cortex and layer CA1 of the hippocampus) in animals in basal condition or submit to an enriched environment. For these two situations, the level of cerebral glucose utilization was quantified by the technique of fluoro-2-deoxyglucose imaging coupled with positron emission tomography (18FDG-PET) only in deficient n-3 PUFA animals. Analysis of brain PUFA content of membrane was performed by gas chromatography and an in vitro approach to primary culture of astrocytes was developed to assess the impact of DHA on metabolic parameters of these cells.The main results show that: - n-3 Deficiency decreases from 67% in membrane DHA content in both brain areas studied. If the deficiency induces mainly a decrease in the specific expression of GLUT1 (-33%) in the fronto-parietal cortex in basal and activation conditions, however it disrupts glutamatergic neurotransmission in the hippocampus by increasing the expression of two glutamate transporters (GLAST and GLT1). In addition, PET data show a general hypometabolism of glucose in animals deficient in n-3 in basal situation. Data collected on the model astrocytes point to a direct effect of DHA on glucose utilization and expression of GLUT1; - DHA supplementation does not alter significantly the membrane content of DHA in both brain areas studied. Unlike the n-3 deficiency, it is clear for the layer CA1 of the hippocampus that the expression of all genes encoding the enzyme complexes of the Krebs cycle and oxidative phosphorylation pathway is significantly increased. These original results suggest the possibility that the fatty acids of the n-3 PUFAs family can act on the energy and functioning of the glutamatergic synapse by modulating 1) glucose metabolism (glucose uptake) and glutamate in deficit intake situation and 2) the production of ATP (oxidative phosphorylation) in DHA supplementation. The alteration of these metabolic parameters during aging and certain neurological disorders, related to a deficit of DHA status, highlight the potential of dietary n-3 PUFA as a preventive factor.

Endocannabinoids are endogenous lipid mediators involved in various biological processes, and have immunomodulatory and anti-inflammatory activities. Anandamide (arachidonoyl ethanolamine, AEA) and 2-arachidonoyl glycerol (2-AG) are the main representatives of this group. The endocannabinoid receptors CB1 and CB2 with AEA have been found in human HaCaT keratinocytes and fibroblasts, but the metabolic pathway leading to endocannabinoid production in the skin has not been fully elucidated. This study aimed to investigate the profile of endocannabinoids and their main metabolizing enzymes in human skin cells and assess whether omega-3 polyunsaturated fatty acids (n-3 PUFA) altered these profiles. In addition, an investigation was carried out to check whether UV radiation could stimulate the production of endocannabinoids and N-acylethanolamines (NAE) in human skin cells. For this purpose HaCaT keratinocytes and 46RB.1N fibroblast cells were treated with 10 and 50µM of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or oleic acid (OA) in the presence or absence of UVR (15mJ/cm2). Data suggest that n-3 PUFA may both directly (by up-regulating NAPE-PLD levels) and indirectly (by decreasing FAAH levels) increased endocannabinoid and NAE levels in HaCaT keratinocytes and 46BR.IN fibroblasts. DHA treatment significantly decreased COX-2 expression in the absence of UVR and inhibited UVR-induced COX-2 overexpression in 46BR.IN fibroblasts. In contrast, DHA appeared to induce COX-2 up-regulation in the absence of UVR and did not prevent UVR induced COX-2 up-regulation in HaCaT keratinocytes. EPA appeared to induce COX-2 down-regulation in the absence of UVR and did not prevent UVR induced COX-2 up-regulation in both HaCaT keratinocytes and 46BR.IN fibroblasts. UVR did not have any significant effect on endocannabinoid and NAE biosynthesis. However, UVR induced endocannabinoid production in some experiments of this study. A clinical study was carried on 16 volunteers from two different ethnic groups and two different skin types. The purpose was to assess the effect of UVR on the serum endocannabinoids and NAE, therefore, the volunteers were subjected to multiple doses (1.3, SED/ 6 min) of UVR for 6 weeks. Data showed that UVR did not have major effect on human serum NAE in both skin phototypes II and V but increased 2-AG in human serum in both skin types but the more pronounced effect was evident in skin phototypes V rather than in skin phototypes II. Human serum docosahxaenoylethanolamide levels were found to be higher in White Caucasians group (skin phototypes II). Based on these it can be concluded that n-3 PUFA and UVR alter the endocannabinoids and NAE profile in HaCaT keratinocytes and 46BR.IN fibroblasts. In addition, results of the clinical study indicated that UVR has no major effects on serum endocannabinoids or NAE therefore, further studies are required to address this question in vivo.