Adipose tissue represents an important endocrine organ that secretes a multitude of adipokines known to mediate inflammation, lipid metabolism, and insulin sensitivity in peripheral tissues such as skeletal muscle. Specifically, adiponectin stimulates skeletal muscle fatty acid oxidation and is associated with improvements in insulin response. Long-chain n-3 polyunsaturated fatty acids (PUFA) are well known for their anti-inflammatory and insulin-sensitizing properties, and their dietary consumption is associated with a more favourable circulating adipokine profile, including increased adiponectin. However, whether n-3 PUFA can directly stimulate adiponectin secretion from human adipocytes, as well as the underlying mechanisms involved, is unknown. In contrast to n-3 PUFA, diets high in saturated fatty acids (SFA) are thought to decrease adiponectin and increase pro-inflammatory adipokines, as well as blunt skeletal muscle response to both adiponectin and insulin, possibly via activation of inflammatory pathways. The role of n-3 PUFA in mediating the communication between adipose tissue and skeletal muscle, as well as preventing SFA-induced impairments in skeletal muscle function, has yet to be examined. In this thesis, it was found that long-chain n-3 PUFA increase adiponectin secretion from human adipocytes via a peroxisome proliferator-activated receptor gamma-dependent mechanism. The effects of n-3 PUFA on adiponectin secretion were additive when combined with the thiazolidinedione, rosiglitazone. Secondly, incorporation of n-3 PUFA into a high SFA diet prevented impairments in adiponectin response and both prevented and restored impairments in insulin response in rodent skeletal muscle. Interestingly, these findings were paralleled by prevention of SFA-induced increases in toll-like receptor 4 expression by n-3 PUFA, suggesting inflammatory changes may be involved. Finally, dietary n-3 PUFA and SFA modulated the secretion of adipose tissue-derived factors from visceral rodent adipose tissue and subsequent exposure of isolated skeletal muscle to such factors induced acute changes in inflammatory gene expression without affecting insulin sensitivity. Together, the findings in this thesis suggest that n-3 PUFA modulate adipokine secretion from adipose tissue and that adipose-derived factors mediate skeletal muscle inflammation and response to adiponectin and insulin. Ultimately, this work highlights the importance of considering n-3 PUFA as a therapeutic strategy in the prevention and treatment of obesity and related pathologies.

Breast cancer molecular subtypes, based on expression of estrogen, progesterone and human epidermal growth factor 2 receptors, alter prognosis and treatment options. α-linolenic acid (ALA) is a complementary therapy, however its effectiveness across breast cancer types and estrogen environments is unclear. This research determined the effect of ALA on growth, apoptosis, fatty acid profile, and gene changes in four breast cancer cell lines with varying receptor expression with or without (±) estradiol (E2). ALA (50-200uM) ± E2 reduced growth in all cell lines. 75μM ALA +E2 increased phospholipid % ALA in all cell lines and induced apoptosis in cell lines lacking the three receptors. Cellular % ALA was positively associated with apoptosis and inversely associated with cell growth. ALA altered expression of cell cycle, apoptosis and signal transduction genes. In conclusion, ALA incorporates into breast cancer cells, reduces growth and induces apoptosis regardless of receptor status or E2 level.

No description available.

Breast cancer molecular subtypes, based on expression of estrogen, progesterone and human epidermal growth factor 2 receptors, alter prognosis and treatment options. α-linolenic acid (ALA) is a complementary therapy, however its effectiveness across breast cancer types and estrogen environments is unclear. This research determined the effect of ALA on growth, apoptosis, fatty acid profile, and gene changes in four breast cancer cell lines with varying receptor expression with or without (±) estradiol (E2). ALA (50-200uM) ± E2 reduced growth in all cell lines. 75μM ALA +E2 increased phospholipid % ALA in all cell lines and induced apoptosis in cell lines lacking the three receptors. Cellular % ALA was positively associated with apoptosis and inversely associated with cell growth. ALA altered expression of cell cycle, apoptosis and signal transduction genes. In conclusion, ALA incorporates into breast cancer cells, reduces growth and induces apoptosis regardless of receptor status or E2 level.

Overproduction of intestinal chylomicrons (CM) has been proposed to contribute to fasting and post-prandial (PP) dyslipidemia and may accelerate the development of cardiovascular disease (CVD) during obesity, insulin resistance (IR) and diabetes. However, the impact of morphological changes in intestinal mucosa structure have not been investigated during IR and intestinal dyslipidemia. The first objective of this thesis was to characterize intestinal villi morphology and to determine whether a morphological relationship exists with enterocytic apoB48 (a marker of CM), and intestinal lymph secretion of apoB48 in the obese and IR JCR:LA-cp rat. The second objective was to assess the impact of n-3 PUFA supplementation on PP dyslipidemia in the JCR:LA-cp rat. Intestinal hypertrophy was observed in IR rats, corresponding to an increase in intestinal and lymphatic apoB48 expression. Further, a dietary intervention of n-3 PUFA showed lower PP plasma concentrations of apoB48 and PP plasma inflammatory markers. We conclude that intestinal hypertrophy may contribute to intestinal CM overproduction during obesity and IR. Additionally, dietary n-3 PUFA improves PP lipemia and the associated PP inflammatory response in the JCR:LA-cp rat model. / Nutrition and Metabolism

The aim of this thesis is to assess the influence of the polyunsaturated fatty acids, especially DHA and EPA in the diet on the animal organism in accordance to the levels of total HDL and LDL cholesterol and triglycerides in plasma. As experimental animals were used rats and they were divided into 3 groups of 10 pieces: control group with the addition of 6 % Carthamus tinctorius (n-6 flares), the group with the addition of 6 % fish oil (n-3: EPA, DHA fish) and the group with 6 % addition of oil from Schizochytrium (n-3: DHA, DHA). After 40 days the animals were putted to death according to relevant regulations. Blood lipids were obtained from blood samples by spectrophotometry. Value of polyunsaturated fatty acids of n-3 and n-6 was set by gas chromatography in the liver, muscle and adipose tissue. In accordance to the increase of content n-3 PUFA in group with fish oil and with oil from Schizochytrium, total and LDL cholesterol was reduced in comparison of samples in control group. In comparison to the control group were TAG reduced only in the group with addition of oil.

The aim of my thesis was to verify the technology of rearing common carp (Cyprinius carpio) with increased levels of omega 3 fatty acids. The technology was tested in 2010 and 2011. A mixture of KP Len and cereal was used for the experiment in 2010. In 2011, the fish were divided into three groups The first group was fed a mixture of KP Len, the second a type of cereal, and the third was kept on natural feed. The technology was carried out under the conditions of the Czech fishery industry. During the entire growing period the course of growth was monitored as part of the framework of regular checks and the parameters of the quality of water was measured. The main descriptive characteristics was the fat content and composition of fatty acids. The combination of KP Len achieved a significantly higher content of PUFA than the group of fish receiving cereals in 2010 and in 2011. When comparing groups of fish fed a mixture of KP Len and those fed natural feed in 2011, no statistically significant differences in PUFA were detected. In 2010 the fish fed a mixture of KP Len reached the highest content of EPA and DHA. On the contrary, in 2011 the significantly highest content was detected in the muscle of fish kept on natural feed.

The work is focused on the nutrition and farming technology influences on the changes of the quality of common carp (Cyprinus carpio L.) and european catfish (Silurus glanis L.) meat. For the first experiment were used 6 groups of fish (common carp). Five of those were fed on cereals (maize, wheat, triticale, rye and barley), the sixth group was left on natural food by way of the control group. For the second experiment were used two groups of fish (european catfish). The first group was bred by the classical technology in fresh water ponds using natural food (dietary fish) by way of the control group. The second group was bred intensively in warm water in controlled conditions using feed compouned. In both of groups were defined following characteristics: weight yield, sensoric analysis, content of nitrogen compounds, fat content and spectrum of fatty acids in fat. It was ascertained that the rearing technology affects the results in all monitored characteristics. The biggest attention was payed to the results of fatty acids spectrum. While in the test using common carp was proved a higher proportion of PUFA (inclusive EPA and DHA) in the control group, in the test using catfish was this proportion higher in intensively reared group.

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Corrigir palavras-chave 1ª letra sempre em maiúsculo ex: Ácidos graxos Microalgas on 2016-05-04T16:46:34Z (GMT) / Submitted by Sandra Raquel Correa (sandracorrea42@hotmail.com) on 2016-05-06T03:33:18Z No. of bitstreams: 1 ana priscila centeno da rosa - produo de biomassa e cidos graxos por diferentes microalgas e condies de cultivo (1).pdf: 1584152 bytes, checksum: 9b24bade17037b2da9a900a3e058896c (MD5) / Approved for entry into archive by dayse paz (daysepaz@hotmail.com) on 2016-05-09T19:04:12Z (GMT) No. of bitstreams: 1 ana priscila centeno da rosa - produo de biomassa e cidos graxos por diferentes microalgas e condies de cultivo (1).pdf: 1584152 bytes, checksum: 9b24bade17037b2da9a900a3e058896c (MD5) / Made available in DSpace on 2016-05-09T19:04:12Z (GMT). No. of bitstreams: 1 ana priscila centeno da rosa - produo de biomassa e cidos graxos por diferentes microalgas e condies de cultivo (1).pdf: 1584152 bytes, checksum: 9b24bade17037b2da9a900a3e058896c (MD5) Previous issue date: 2012 / Devido a sua composição bioquímica, as microalgas apresentam o potencial de serem adicionadas diretamente a alimentos e ração animal, ou indiretamente por meio da adição dos biocompostos produzidos pelas mesmas. Além disso podem ser utilizadas na biofixação de CO2 e na produção de biocombustíveis. O objetivo deste trabalho foi produzir biomassa e ácidos graxos por diferentes microalgas e condições de cultivo. Para o desenvolvimento do trabalho, este foi dividido em três etapas: (i) avaliação da influência da atenuação da intensidade luminosa na produção e composição da microalga Tetraselmis suecica F&M-M33; (ii) avaliação do crescimento e produção de ácidos graxos pela microalga Nannochloropsis oculata em cultivos autotróficos e mixotróficos; e (iii) avaliação do crescimento e produção de ácidos graxos pelas microalgas Chlorella vulgaris e Chlorella kessleri em cultivos autotróficos e mixotróficos. No cultivo da microalga T. suecica F&M-M33 a produtividade foi influenciada pela concentração celular mantida nos cultivos bem como pela radiação solar incidida. Quando os ensaios foram realizados em fotobiorreatores inclinados, estes apresentaram produtividade máxima de 0,96 g.L-1 .d-1 . Quando realizados em GWP verticais, dispostos paralelamente, a produtividade máxima obtida foi 0,45 g.L- 1 .d-1 . As máximas concentrações proteicas (49,87 a 51,01%) e lipídicas (22,03 a 23,36%) foram obtidas quando a microalga foi cultivada nos fotobiorreatores verticais e dispostos paralelamente sem interferência de sombreamento nas laterais. Para a microalga N. oculata foram realizados 2 planejamentos fatoriais 2 3 , em que foram variadas a temperatura, concentração de nitrato no meio de cultivo e fonte de carbono. Os máximos valores para o crescimento celular e produtividade foram obtidos no cultivo mixotrófico (0,64 g.L-1 e 141,95 mg.L-1 .d-1 , respectivamente), quando a microalga N. oculata foi cultivada em meio F/2 utilizando 1 g.L-1 de glicose como fonte orgânica de carbono, 75 mg.L-1 de NO3 e 20 ºC. Para o cultivo autotrófico as máximas concentração celular e produtividade (0,62 g.L-1 e 69,78 mg.L-1 .d-1 , respectivamente) foram obtidas quando a microalga foi cultivada com 1 g.L-1 de NaHCO3, 10 mg.L-1 de NO3 e 20 ºC. Os principais ácidos graxos encontrados em ambos os cultivos foram o ácido mirístico (C14:0), ácido palmítico (C16:0), ácido palmitoleico (C16:1), ácido oleico (C18:1) e ácido eicosapentaenoico (EPA, C20:5-3), destacando-se o ácido palmítico (C16:0) que apresentou concentrações de 21,4 a 47% do total dos ácidos graxos analisados. As microalgas Os cultivos das microalgas C. vulgaris e C. kessleri foram avaliados utilizando metodologia de Planejamento Experimental Plackett Burman. A microalga C. vulgaris apresentou concentração celular máxima (0,97 g.L-1 ) no cultivo autotrófico, com fotoperíodo 24 h claro e 6% de CO2. A máxima produtividade (180,68 mg.L-1 .d-1 ) foi obtida no cultivo mixotrófico para C. vulgaris cultivada com 1 g.L-1 de NaHCO3 e 5 g.L-1 de resíduo industrial de oleaginosas (RIO). O ácido palmítico (C16:0) foi o ácido graxo obtido em maiores concentrações tanto para os cultivos autotróficos (21,22 a 53,78%) como para os mixotróficos (25,43 a 45,98%). A concentração de ácidos graxos poliinsaturados (PUFA) variou de 12,19 a 41,17% nos cultivos autotróficos e de 10,98 a 34,26% nos cultivos mixotróficos, mas não foi afetada significativamente (p<0,05) pela microalga utilizada, podendo tanto a C. vulgaris como a C. kessleri serem utilizadas como fonte de ácidos graxos saturados e insaturados. / Due to its biochemical composition, microalgae are a potential group to be added directly, or indirectly by the addition of microalgae produced biocompounds, in food and feed. In addition, while producing the biomass, the culture may be utilized in carbon dioxide biofixation, as well as the final biomass can be directed to second generation biofuels production. The aim of this work was to produce biomass and fatty acids by different microalgae and growing conditions. To develop this work, it was divided into three stages: (i) light mitigation influence in Tetraselmis suecica F&M-M33 production and composition; (ii) growth profile and fatty acids production evaluation by the microalgae Nannochloropsis oculata in autotrophic an mixotrophic cultures; and (iii) growth profile and fatty acids production evaluation by the microalgae Chlorella vulgaris and Chlorella kessleri in autotrophic an mixotrophic cultures. In the T. suecica F&MM33 culture, the productivity was influenced by solar radition and the cultures cellular concentrations. When the cultures were realized in inclined photobioreactor the productivity achieved maximum values of 0.96 g.L-1 .d-1 . When the cultures were realized in vertical GWP arranged in parallel, maximum achieved productivity was 0.45 g.L-1 .d-1 . Maximum protein (49.87 a 51.01%) and lipid (22.03 a 23.36%) concentrations were obtained in cultures with vertical photobioreactors arranged in parallel, avoiding shadow interference among themselves. To the microalgae N. oculata were carried out two 2³ factorial design, where the studied variables were temperature, nitrate concentration in the medium and carbon source. The highest growth rate and biomass productivity were achieved in the mixotrophic culture (0.64 g.L-1 and 141.95 mg.L-1 .d-1 , respectively), when the microalgae N. oculata was cultivated in F/2 media utilizing 1 g.L-1 of glucose as carbon source, 75 mg.L-1 of NO3 and 20 °C. In the autotrophic culture, maximum cellular concentration and productivity culture (0.62 g.L-1 and 69.78 mg.L-1 .d-1 , respectively) were obtained when the microalgae was cultivated 1 g.L-1 of NaHCO3, 10 mg.L-1 of NO3 and 20 °C. The main fatty acids present in the cultures were the myristic acid (C14:0), palmitic acid (C16:0), palmitoleic acid (C16:1), oleic acid (C18:1) and eicosapentaenoic acid (EPA, C20:5-3), with emphasis on C16:0, which appeared in the highest concentrations, representing 21.4 and 47% of the analyzed fatty acids. The culture of C. vulgaris and C. kessleri were evaluated trough a Plackett Burman Experimental Design. The microalgae C. vulgaris presented maximum cellular concentration (0.97 g.L-1 ) in the autotrophic culture with 24 h photoperiod bright/dark and 6% of CO2. Maximum productivity (180.68 mg.L-1 .d-1 ) was obtained by C. vulgaris mixotrophic culture with 1 g.L-1 of NaHCO3 and 5 g.L-1 of industrial waste oilseeds (RIO). The palmitic acid (C16:0) was the fatty acid with the highest concentration in the autrophic culture (21.22 a 53.78%) as well as in the mixotrophic (25.43 a 45.98%). The polyunsaturated fatty acid concentration varied between 12.19 and 41.17% in the autotrophic cultures and between 10.98 and 34.26% in the mixotrophic cultures. However, its production was not statistically affected (p<0,05) by the utilized microalgae. Therefore, both microalgae, C. vulgaris and C. kessleri¸ may be utilized as a saturated and unsaturated fatty acid source.

Le cerveau est très riche en acide docosahexaénoique (DHA, acide gras polyinsaturé (AGPI) n-3) et en acide arachidonique (AGPI n-6) qui sont de puissants immunomodulateurs. Ils pourraient être impliqués dans le contrôle de la neuroinflammation via leur conversion en dérivés lipidiques bioactifs. Dans ce contexte, notre objectif était de définir le rôle des médiateurs lipidiques dérivés des AGPI n-3 possédant des propriétés anti-inflammatoires et pro-résolutives dans la régulation de l’inflammation au niveau du cerveau. Nous avons d’abord caractérisé l’impact d’une modulation nutritionnelle en AGPI n-3 sur la composition lipidique cérébrale. Dans un modèle d’inflammation cérébrale, la consommation d’AGPI n-3 induit 1) une augmentation des métabolites lipidiques dérivés des AGPI n-3, 2) une diminution des métabolites lipidiques dérivés des AGPI n-6, et 3) une diminution de l’inflammation dans l’hippocampe. De plus, un apport en AGPI n-3 au cours de la période périnatale n’affecte pas la composition lipidique des cellules immunitaires du cerveau, les cellules microgliales. Ensuite, nous avons choisi une approche thérapeutique afin de démontrer in vitro dans un modèle de cellules microgliales que la RvD1, dérivée du DHA, en se fixant à son récepteur ALX/Fpr2, atténue l’inflammation via la régulation de la voie NFκB et de microARN. In vivo, l’injection i.c.v. de la RvD1 et du DHA atténue l’inflammation dans l’hippocampe par des processus différents. Les dérivés lipidiques bioactifs issus des AGPI n-3 pourraient être les médiateurs par lesquels les AGPI n-3 exercent leur effet bénéfique sur la régulation de l’inflammation au niveau du cerveau, la RvD1 étant fortement impliquée. / The brain is highly enriched in docosahexaenoic acid (DHA, n-3 polyunsaturated fatty acid, PUFA) and in arachidonic acid (n-6 PUFA) that are strong immunomodulators. They could be involved in the regulation of neuroinflammation through their conversion into bioactive lipid derivatives. Then, our objective was to define the role of n-3 PUFA derived lipid mediators that have anti-inflammatory and pro-resolutive properties in the regulation of brain inflammation. First, we characterized the impact of dietary n-3 PUFA modulation on brain lipid composition. In a central inflammatory model, n-3 PUFA intake induced 1) an increase in n-3 PUFA-derived lipid mediators, 2) a decrease in n-6 PUFA-derived lipid mediators, and 3) a decrease in inflammation in the hippocampus. Moreover, n-3 PUFA intake during the perinatal period did not affect lipid composition of brain immune microglial cells. Then, we chose a therapeutic approach to demonstrate in vitro in microglial cells that RvD1 derived from DHA, through the binding on its receptor ALX-Fpr2, attenuated inflammation via the regulation of NFκB pathway and microRNA expressions. In vivo, intracerebral injection of RvD1 and DHA reduced inflammation in the hippocampus by different pathways. Thus, the bioactive lipid derivatives from n-3 PUFA could be the mediators by which n-3 PUFA exert their beneficial effects on neuroinflammation, RvD1 playing a crucial role in this regulation.