Förlust av muskelmassa med åldrande försämrar den fysiska funktionen, vilket även minskarlivskvaliteten och kan leda till svaghet och för tidig död. Omega-3-fettsyror stimulerar protein-anabolism och kan därför vara användbart för att förebygga och behandla sarkopeni. Syfte:Syftet med denna studie var att utvärdera effekten av omega-3-fettsyra-tillskott på graden avmuskelproteinsyntes hos vuxna. Metod: Studien är utförd som en litteraturstudie där relevantavetenskapliga och publicerade studier utvärderats och dess resultat har analyserats för attbesvara studiens syfte. Studiernas relevans bedömdes utifrån artiklarnas titel och abstrakt. 234studier i Onesearch, 5 studier i PubMed gicks igenom till en början. 30 abstrakt lästes, 21studier lästes i fulltext, 7 studier baserat på in- och exklusionskriterierna valdes ut till studienefter läst fulltext. Resultat: De flesta studier har utvärderat effekten av omega-3-tillskott hosyngre vuxna 18-30 år och äldre vuxna 65 år och äldre. Även om det finns en relativ brist påstudier som utvärderar effekten av omega-3-tillskott på muskelproteinsyntes (MPS) hos vuxna30-70 år, verkar det som om omega-3 kan främja anabola ökningar vid styrketräning hos äldreindivider. Slutsats: Ytterligare forskning behövs inom detta område för att dra relevantaslutsatser. Denna litteraturstudie drar slutsatsen att omega-3-fettsyror stimulerar syntesen avmuskelprotein hos vuxna och kan vara användbart för att förebygga och behandla sarkopeni. / Loss of muscle mass with aging impairs physical functions, but also reduces quality of life andcan lead to weakness and premature death. Omega-3 fatty acids stimulate protein anabolism andmay therefore be usefull to treat sarcopenia. Purpose: The aim of this study was to evaluate theeffect of omega-3 fatty acid supplements on the degree of muscle protein synthesis in adults.Metod: The study is conducted as a literature study where relevant scientific and publishedstudies, evaluations and its results have been analyzed to answer the purpose of the study. Therelevance of the studies were assessed on the basis of the title and abstract of the articles. 234studies in Onesearch, 5 studies in PubMed were initially reviewed. 30 abstracts were read, 21studies were read in full text, based on the inclusion and exclusion criteria 7 studies wereselected for the study after reading in full text. Results: Most studies have evaluated the effect ofomega-3 supplements in younger adults (18-30 years) and older adults (65 years and older).Although there is a relative lack of studies evaluating the development of omega-3 supplementson MPS in adults 30-70 years, it seems that omega-3 can promote anabolic increases in olderindividuals. Couclusion: Further research is needed in this area to draw relevant conclusions.This literature review concludes that omega-3 fatty acids stimulate the synthesis of muscleprotein in adults and may be useful to prevent and treat sarcopenia.

El sector pesquero a lo largo de los años ha tenido fases de expansión y crisis que evidencian la problemática de la industria, la cual es el sobredimensionamiento de flota y planta; esto conllevó a la sobre explotación de la biomasa anchovetera y la ineficiencia de los agentes económicos en sus operaciones. Es por eso que en el año 2008, se promulga el Decreto Legislativo 1084, a través del cual se estableció el nuevo sistema de Límites Máximos de Captura por Embarcación (LMCE), este nuevo régimen entra en vigencia la primera temporada del 2009 y rige sólo para la anchoveta que se destina al consumo humano indirecto (CHI), es decir, para la anchoveta que es utilizada para la elaboración de harina y aceite de pescado. Esta norma introdujo cuotas individuales de pesca de anchoveta y se las asignó a las embarcaciones que ya operaban en esta pesquería, con la cual se eliminó el sistema anterior que se basaba en las cuotas globales de capturas, las cuales incentivaba a que se dé la “Carrera Olímpica” (pesca desmedida) para obtener la mayor cantidad del recurso posible. Para analizar la repercusión del Decreto Legislativo 1084, el presente trabajo propone evaluar el comportamiento pre y post reforma del sector de los años 2005 hasta 2014, con la finalidad de demostrar la eliminación de la pesca desmedida y mejora de calidad en los desembarques de anchoveta. Los resultados obtenidos después de la investigación realzan lo importante que fue la implementación del Decreto Legislativo 1084 en el sector pesquero, presentando mejoras en el ordenamiento del sector que se ve reflejado en el desarrollo de la industria pesquera. / The fishing sector over the years has had phases of expansion and crisis that show that the problem of the industry is the oversizing of the fleet and plant, this led to the over exploitation of anchovy biomass and that the economic agents are less efficient in their operations. That is why, in 2008, Legislative Decree 1084 is enacted, through which it was established the new system of Maximum Limits of Capture by Vessel (MLCV), this regime comes into force in the first season of 2009 and which governs only anchovy intended for indirect human consumption (IHC), that is, for the anchovy that is used for the production of fish meal and fish oil. This standard introduced individual anchovy fishing quotas and allocated it to vessels already operating in this fishery, thereby eliminating the previous system, which set a global catch quota, which encouraged the "Olympic Race" to get as much of the resource as possible. In order to analyze the impact of Legislative Decree 1084, the present research proposes to evaluate the pre and post reform behavior of the sector, in order to demonstrate that overfishing was eliminated and that a better quality of the anchovy landings was generated. The results obtained after the investigation highlight the importance of the implementation of Legislative Decree 1084 in the fishing sector, presenting improvements in the ordering of the sector that is reflected in the development of the fishing industry / Trabajo de Suficiencia Profesional

Avaliamos no presente estudo: 1) os efeitos do desuso das patas traseiras de ratos por duas semanas sobre as vias de sinalização de síntese e degradação de proteínas no músculo sóleo e a administração de óleos de peixe ricos em eicosapentaenóico (EPA) ou docosaexaenóico (DHA) e 2) as alterações induzidas pelo desuso no músculo sóleo em camundongos FAT-1. Concluímos que, apesar da variação pequena na razão ácidos graxos ômega-6/ômega-3, efeitos significativos da oferta aumentada de ácidos graxos ômega-3 foram observados na área de seção transversa e vias de sinalização relacionadas à síntese e degradação de proteínas no músculo sóleo nos dois protocolos. / We investigated herein: 1) the effects skeletal muscle disuse atrophy induced by two-week hind limb suspension (HS) on protein synthesis and degradation signaling in soleus muscle and the administration of either eicosapentaenoic (EPA) or docosahexaenoic (DHA)-rich fish oil supplementation, and 2) the changes induced by hind limb disuse on soleus muscle of Fat-1 transgenic mice. We concluded that, in spite of the small variation in the omega-6/omega-3 fatty acid ratio, significant effects of the increased omega-3 fatty acid levels were observed on the CSA and signaling pathways associated with soleus muscle protein synthesis and degradation in both experimental protocols.

Introdução: Os efeitos metabólicos do uso combinado dos triglicerídeos de cadeia média (TCM) e do óleo de peixe (OP) na esteatose hepática ainda não estão totalmente esclarecidos. Objetivo: O presente estudo teve o objetivo de verificar os efeitos da combinação dos TCMs e OP na esteatose hepática e estresse oxidativo induzidos pela dieta hiperlipídica (HL+) termolizada em ratos. Material e Métodos: Foram utilizados no total 50 ratos machos da linhagem Wistar. O grupo Controle (n=10) recebeu a dieta controle. Os grupos HL+ receberam a dieta contendo 50% de gordura animal (GA) termolizada e 50% de ração. A adaptação às dietas HL+ foi realizada durante 5 dias. Os grupos HL+GA, HL+TCM, HL+OP e HL+TCM/OP (n=10) receberam a dieta HL+ com 50% de lipídios (gordura animal termolizada) durante 30 dias. Após este período, os grupos HL+TCM, HL+OP e HL+OP/TCM receberam as dietas HL+ adicionadas de óleo de TCM (OTCM), OP e OTCM + OP, respectivamente, durante 20 dias. As análises realizadas foram a gordura hepática total, frações lipídicas hepáticas e séricas, glicemia, vitamina E e retinol séricos, glutationa reduzida (GSH) e malondialdeído (MDA) sérico e hepático e aminotransferases séricas. Resultados: Os grupos HL+ apresentaram acúmulo significativo de gordura total e triglicerídeos hepáticos, exceto o HL+OP. Apenas o grupo HL+TCM não apresentou acúmulo significativo de colesterol total hepático (CT). Este mesmo grupo apresentou valores maiores de CT e HDLcol séricos e menor razão triglicerídeos/HDLcol. Os valores séricos de aminotransferases foram significativamente maiores nos grupos que receberam os OTCM e/ou OP. A peroxidação lipídica (LPO) hepática foi maior foi nos grupos HL+, exceto o HL+TCM. Apenas o grupo HL+GA apresentou maior LPO sérica. Verificou-se que a GSH foi maior nos grupos HL+GA, HL+TCM e HL+OP/TCM, a vitamina E sérica foi menor nos grupos HL+GA, HL+OP e HL+OP/TCM e o retinol sérico foi maior nos grupos HL+GA e HL+TCM. Conclusões: As alterações séricas não refletiram as alterações hepáticas em relação aos lipídios, estresse oxidativo e antioxidantes. O uso do óleo de TCM e óleo de peixe em associação na dieta HL+ resultou em efeito negativo devido ao maior acúmulo de gordura hepática tanto na forma de triglicerídeos quanto de colesterol, maior peroxidação lipídica hepática e menor vitamina E sérica. / Introduction: The metabolic effects of combined use of medium chain triglycerides (MCT) and fish oil (FO) on non alcoholic hepatic steatosis are not fully understood. Objective: The aim of this study was to investigate the effects of the combination of MCT and FO on hepatic steatosis and oxidative stress induced by high fat (HF+) thermolyzed diet in rats. Methodology: Fifty wistar male rats were studied. The Control group (n = 10) received the standard diet. The HF+ groups received diet with 50% of thermolyzed animal fat (AF) and 50% of ration. Five days were dedicated for adaptation to high-fat diets. The groups HF+AF, HF+MCT, HF+FO and HF+MCT/FO (n = 10) received HF+ diet with 50% thermolyzed fat during 30 days. After this period, the groups HF+MCT, HF+FO and HF+MCT/FO received HF+ diets with MCT oil (MCTO), FO and MCTO + OP, respectively, during 20 days. Analysis of total liver fat, liver and serum lipid fractions, serum glucose, vitamin E and retinol, serum and liver reduced glutathione (GSH) and malondialdehyde (MDA), and serum aminotransferases (AST and ALT) were performed. Results: The groups HF+ showed higher total fat and triglycerides, except HF+FO. Only HF+MCT group didn´t have higher liver total colesterol (TC). This same group had higher serum TC and HDLcol and lower triglycerides/HDLcol ratio. The groups fed with MCTO and/or FO had higher serum aminotransferase. Liver lipid peroxidation (LPO) was higher in HF+ groups, except HF+MCT. Serum LPO was higher in HF+AF. The hepatic GSH was higher in the groups HF+AF, HF+MCT and HF+MCT/FO, serum vitamin E was lower in groups HF+AF, HF+FO and HF+MCT/FO, and serum retinol was higher in groups HF+AF and HF+MCT. Conclusions: Lipids, oxidative stress and antioxidant serum and liver alterations didnt correspond. The association of MCTO with FO in HF+ diet resulted in a negative effect when it concerns liver fat, triglyceride and cholesterol accumulation, higher liver lipid peroxidation and lower serum vitamin E.

A manipulação da dieta constitui uma prática efetiva e rápida de alteração da composição do leite, especialmente do seu teor de gordura. Entretanto, os mecanismos envolvidos não são ainda completamente conhecidos, embora muito se tenha avançado na última década. Sabe-se hoje que certo tipo de ácido graxo (CLA trans-10 cis-12) formado no rúmen sob condições específicas de alimentação é capaz de inibir a síntese de gordura do leite. Entretanto, depressão da gordura do leite (DGL) tem sido observada em casos (e.g. dietas contendo óleo de peixe) onde não há formação deste inibidor. Embora o efeito do CLA sobre a secreção de gordura do leite já esteja bem caracterizado, estudo prévio conduzido pelo nosso grupo mostrou ainda um aumento do teor de proteína do leite em resposta a este tratamento. Dois experimentos foram conduzidos com os seguintes objetivos principais, respectivamente: 1) determinar se um maior suprimento de proteína através da dieta afeta a secreção de proteína do leite de vacas recebendo CLA e 2) Estudar os mecanismos envolvidos na DGL de vacas recebendo dietas contendo óleo de peixe (OP) e níveis distintos de fibra. No primeiro experimento, 48 vacas em lactação receberam os seguintes tratamentos: 1) Dieta controle (DC) + Lac100, 2) DC + CLA, 3) Dieta com alta proteína (DAP) + Lac100 e 4) DAP + CLA. O Lac100 (sais de cálcio de óleo de soja) foi utilizado como placebo. O CLA foi protegido por encapsulação e o produto utilizado continha ~16% de CLA. No segundo experimento, 12 vacas em lactação foram avaliadas em 3 períodos: a) Basal: os animais receberam uma dieta com alto teor de fibra sem OP (dieta basal) por 12 dias; b) Suplementação: 4 vacas/grupo receberam os seguintes tratamentos: 1) Dieta com alta fibra + OP (AF+OP), 2) Dieta com baixa fibra sem OP (BF) e 3) Dieta com baixa fibra + OP (BF+OP); c) Pós-suplementação: todos os animais passaram a receber novamente a dieta basal por 12 dias. Os resultados obtidos no primeiro experimento mostraram que o CLA não foi eficientemente protegido, de forma que a redução da secreção de gordura do leite foi de pequena magnitude em relação a outros trabalhos. Da mesma forma, a proteção dos sais de cálcio de óleo de soja foi pequena, resultando em maior concentração de CLA cis-9 trans-11 (P<0,05) e menor concentração de ácido linoléico (P<0,05) no leite dos animais. Apesar da concentração do CLA trans-10 cis-12 no leite ter aumentado igualmente em resposta ao CLA e ao Lac100, o teor de gordura do leite foi menor (P<0,05) no primeiro tratamento, sugerindo a presença de outros inibidores (ou precursores) no produto utilizado. A concentração de CLA trans-10 cis-12 no leite explicou ~50% da variação da DGL, sugerindo que outros fatores afetaram a síntese de gordura do leite. Os resultados do segundo experimento demostraram, de forma inédita, que o CLA trans-9 cis-11 e o C18:1 cis-11 estão estreitamente relacionados à DGL dos animais que receberam OP. A DGL foi causada por uma ampla redução (P<0,01) da secreção tanto dos ácidos graxos sintetizados de novo quanto dos pré-formados, sugerindo que o mecanismo da DGL pode envolver a inibição de diferentes enzimas lipogênicas. O menor (P<0,01) índice de atividade da enzima &#8710;-9 dessaturase em animais que receberam OP é consistente com a idéia acima. Diferentemente do observado em resposta ao OP, a secreção de gordura do leite não foi afetada pelo tratamento BF (P>0,1). Os teores de proteína e lactose aumentaram na dieta BF e nas dietas contendo OP, respectivamente. / Diet manipulation is an effective and rapid way to change milk composition, mainly for fat content. However, mechanisms are not fully undestood in despite of progress in the area over the last decade. Nowadays, it is known that a molecule of fatty acid (CLA trans-10 cis-12) which is formed in the rumen under specific feeding situations is capable of inhibiting milk fat synthesis. However, milk fat depression (MFD) has been observed even at conditions where there is no formation of trans-10 cis12 CLA (e.g. fish oil-supplemented diets). Although CLA effects on milk fat synthesis are well-established, previous study from our group also showed an increase on milk protein content in cows fed CLA. Two trials were conducted with two main objectives: 1) to determine if an additional supply of diet protein affects milk fat synthesis in cows fed CLA and 2) to study the mechanisms involved in MFD of cows fed diets with fish oil (FO) and different fiber levels. In the first trial, 48 lactating cows received the treatments as follow: 1) Control Diet (CD) + Lac100, 2) CD + CLA, 3) High Protein Diet (HPD) + Lac100 and 4) HPD + CLA. The Lac100 (calcium salts of soybean oil) was used as a placebo. CLA was protected by encapsulation (prills) and the product contained 16% CLA. In the second trial, 12 lactating dairy cows were evaluated in three periods: a) Basal: for 12 days, all cows received a baseline diet (High fiber without FO); b) Suplementation: 4 cows/group received the treatments for 21 days: 1) High fiber diet + FO (HF+FO); 2) Low fiber diet without FO (LF) and 3) Low fiber diet + FO (LF+FO); c) Post-supplementation: cows returned to baseline diet on 12 days. Results from the first trial showed that CLA protection method was innefficient. Thus, milk fat reduction was smaller than in other studies. Protection of calcium salts of soybean oil was also small which resulted in higher cis-9 trans-11 CLA and lower linoleic acid concentrations (P<0.05) in milk from cows fed Lac100. In despite of similar milk trans-10 cis-12 CLA increase in response to CLA and Lac100, milk fat content was lower (P<0.05) in cows fed CLA. It suggests the presence of other fat inhibitors (or precursors) in the product containing CLA isomers. Moreover, concentration of milk trans-10 cis-12 CLA explained ~50% of MFD suggesting others factors influencing milk fat synthesis. Results of the second trial were inedit in showing the close association of milk trans-9 cis-11 CLA and C18:1cis-11 concentrations and FO-induced MFD. MFD resulted from a lower (P<0,01) secretion of both de novo and preformed milk fatty acids. It suggests that mechanisms of FO-induced MFD must involve the inhibition of different lipogenic enzymes. The lower (P<0.01) dessaturase activity index in cows fed FO is consistent with this hypothesis. In contrast to FO, milk fat secretion was unchanged (P>0.1) by LF diet which is consistent with low CLA trans-10 cis-12 and C18:1trans-10 concentrations in milk from cows fed this diet. Contents of milk protein and milk lactose increased (P<0.05) in cows fed LF and FO diets, respectivelly.

Introdução: Devido a diversos fatores, recém-nascidos prematuros, em sua maioria, necessitam de nutrição parenteral e uma fonte lipídica que possua um equilíbrio entre os variados tipos de ácidos graxos. SMOFlipid® 20%, uma nova emulsão lipídica pode ser mais adequada para esse equilíbrio. Objetivo: Avaliar o perfil de incorporação de ácidos graxos em eritrócitos de prematuros recebendo essa nova emulsão lipídica, comparada com outra emulsão baseada em óleo de soja. Métodos: Em um ensaio clinico controlado randomizado duplo cego avaliou-se 47 recém-nascidos pré-termo que receberam nutrição parenteral SMOFlipid® 20% (n=25) ou LIPOVENOS® MCT 20% (n=22). Foram avaliados parâmetros laboratoriais, clínicos, demográficos e o perfil de incorporação de ácidos graxos na membrana de eritrócitos. Resultados: Os parâmetros clínicos e demográficos como peso, perímetro cefálico, comprimento, idade gestacional e índice de Apgar não diferiram entre os grupos. Os valores de triglicerídeos e da lipoproteína de muito baixa densidade (VLDL) foram estatisticamente maiores no grupo SMOFLIPID® 20%. Níveis de Aspartato aminotransferase (AST) foram menores em ambos os grupos e os níveis de bilirrubina total e frações não tiveram diferenças. A emulsão SMOFlipid® 20% aumentou os níveis dos ácidos docosa-hexaenoico DHA (C 22:6 w3) e Eicosapentaenoico EPA (C 20:5 w3) na membrana dos eritrócitos. Conclusões: Neste grupo de recém-nascidos pré-termos, essa nova emulsão lipídica, além de mostrar segurança, contribuiu para uma mudança benéfica no perfil de incorporação de ácidos graxos nas membranas celulares, principalmente DHA e EPA / Introduction: Due to several factors, premature newborn infants, in most cases, require parenteral nutrition and a lipid source with balance among the different types of fatty acids. SMOFlipid® 20%, a new lipid emulsion may be more appropriate for this balance. Objectives: To evaluate the profile of fatty acids incorporation in erythrocytes of premature newborn infants receiving this new lipid emulsion compared with an emulsion based on soybean oil. Methods: In a randomized, controlled, double-blind clinical trial, 47 preterm newborn who received parenteral nutrition SMOFlipid® 20% (n=25) or Lipovenos MCT® 20% (n=22) were evaluated. Laboratorial, clinical and demographic parameters and the profile of incorporation of fatty acids in the erythrocyte membrane were evaluated. Results: The clinical and demographic parameters such as weight, head circumference, length, gestational age, and Apgar scores did not differ between the groups. The values of triglycerides and lipoprotein of very low density (VLDL) were statistically higher in the SMOFlipid® 20% group. Levels of aspartate aminotransferase (AST) were lower in both groups and levels of total bilirubin and fractions had no differences. The SMOFlipid® 20% emulsion increased the levels of the docosahexaenoic acid (DHA) and eicosapentaenoic (EPA) acid in the erythrocytes membrane. Conclusions: In this group of preterm newborn infants, this new lipid emulsion, besides showing security, contributed to a beneficial change in the incorporation profile of fatty acids cell membranes, especially DHA and EPA

Estudos realizados em nosso laboratório encontraram que o aumento do conteúdo corporal de ácidos graxos N3, pela produção endógena via modificação genética, protege camundongos do ganho de peso corporal e obesidade induzida por dieta hiperlipídica. Objetivo: Investigar os mecanismos pelos quais o óleo de peixecontrola o balanço energético de camundongos C57BL6/J e UCP1selvagens e Knockout (KO) protegendo do desenvolvimento da obesidade induzida por dieta, com ênfase nos processos termogênicos dependentes e independentes da UCP1. Materiais e Métodos: Protocolo 1- Camundongos C57BL6/J alimentados por 8 semanas com dieta normal (DN) contendo 10% de lipídeos oriundos do óleo de soja e banha de porco, dieta normal N3 (DNN3) contendo 10% de lipídeos oriundos do óleo de soja e óleo de peixe, dieta hiperlipídica (HFD) contendo 60% de lipídeos oriundos do óleo de soja e banha de porco e dieta hiperlipídica (HFDN3) contendo 60% de lipídeos oriundos do óleo de soja e óleo de peixe foram avaliados para o peso corporal, a eficiência energética, a ingestão alimentar, a calorimetria indireta, a adiposidade, a tolerância à glicose e à insulina, o consumo de oxigênio tecidual e a análise lipidômica do tecido adiposo inguinal (TAI) e marrom (TAM). Protocolo 2- Camundongos selvagens e Knockout para a UCP1 alimentados por 8 semanas com dieta (HFD) e (HFDN3) foram avaliados para o peso corporal, a eficiência energética, a ingestão alimentar, a calorimetria indireta, a adiposidade, a tolerância à glicose, e o consumo de oxigênio tecidual. Resultados: Protocolo 1- Não houve diferenças significativas no ganho de peso, adiposidade, ingestão alimentar, consumo de oxigênio e tolerância à glicose entre camundongos C57BL6/J alimentados com as dietas DN e DNN3. Entretanto, aqueles alimentados com dieta HFDN3, apresentaram reduzido ganho de peso corporal, massa dos tecidos adiposos e eficiência energética quando comparados a camundongos alimentados com dieta HFD. Esses efeitos aconteceram na ausência de alterações significativas na ingestão alimentar medida tanto em gramas quanto em Kcal entre esses grupos. Corroborando a menor eficiência energética, camundongos C57BL6/J alimentados com dieta HFDN3 apresentaram maior consumo de oxigênio e similar atividade locomotora espontânea que camundongos alimentados com dieta HFD. Demonstramos que o consumo de oxigênio do TAI foi maior no grupo HFDN3 quando comparado ao grupo HFD. Por fim, a análise lipidômica do TAI e TAM revelou que a principal modificação ocorreu no enriquecimento dos triacilgliceróis (TAG) desses tecidos, sobretudo um aumento de ácidos graxos altamente insaturados (HUFA) nos TAG de camundongos alimentados com dieta HFDN3. Protocolo 2- Demonstramos que a dieta HFDN3 protege os camundongos UCP1 KO contra o ganho de peso corporal, aumenta o gasto energético e melhora à tolerância à glicose de maneira independente da UCP1. Além disso, observamos que o grupo UCP1 KO HFD aumentou a massa do TAM quando comparado aos outros grupos. Conclusão: A substituição da banha de porco pelo óleo de peixe na dieta aumenta o gasto energético de camundongos reduzindo o ganho de peso corporal e a adiposidade de maneira independente da UCP1. Digno de nota, o enriquecimento dos TAG com HUFA, pode ser um importante fenótipo para respostas observadas no balanço energético do grupo HFDN3 de ambos os protocolos. Acreditamos, em parte, que uma alta mobilização dos HUFA para a beta-oxidação possa estar acontecendo em paralelo com a ativação de vias alternativas de gasto energético. Os mecanismos responsáveis por estas ações serão investigados futuramente. / We have previously shown that diet-induced obesity is prevented by increasing N3 fatty acids content in the body of mice through genetic modification. Aim: In the present study, we investigated the mechanisms by which the fish oil control the energy balance protecting mice from diet-induced obesity, with emphasis at shivering and non-shivering thermogenesis. Materials and Methods: Protocol 1- C57BL6/J mice were fed during 8 weeks with normal diet (DN) containing 10% of lipids from soy oil and lard, normal diet N3 (DNN3) containing 10% of lipids from soy and fish oils, high fat diet (HFD) 60% of lipids from soy oil and lard and high fat diet (HFDN3) containing 60% of lipids from soy and fish oils. The evaluated parameters were body weight, energy efficiency, food intake, indirect calorimetry, adiposity, glucose and insulin tolerance, tissue oxygen consumption and lipidomic analysis of the white adipose tissue (WAT) and brown adipose tissue (BAT). Protocol 2- Wild type (WT) and UCP1 knockout (KO) mice were fed during 8 weeks with HFD and HFDN3. In Protocol 2, body weight, energy efficiency, food intake, indirect calorimetry, adiposity, glucose tolerance and tissue oxygen consumption were evaluated. Results: Protocol 1- No significant differences were observed in body weight, adiposity, food intake, oxygen consumption and glucose tolerance between mice fed with DN and DNN3. Mice fed with HFDN3, however, displayed reduced body weight gain, epididimal, inguinal and retroperitoneal adipose tissue masses, and energy efficiency when compared to mice fed with HFD. These effects occurred in the absence of significant alterations in food intake measured in grams and Kcal. Corroborating the decrease in energy efficiency, C57BL6/J mice fed with HFDN3 have increased oxygen consumption, but similar spontaneous locomotor activity when compared to mice fed with HFD. We show that oxygen consumption in the WAT in mice fed with HFDN3 was higher than in mice fed with HFD. Finally, the lipidomics analysis in both WAT and BAT revealed an enrichment of the triacylglycerol (TAG) linked to highly unsaturated fatty acids (HUFA, 46 double bonds) in mice fed with HFDN3. Protocol 2- The HFDN3 protects both WT and UCP1 KO groups from body weight gain, increases energy expenditure, and improves glucose tolerance. Moreover, we observe that UCP1 KO HFD group increased the weight of the TAM relative to the other groups. Conclusion: Our results indicate that replacement of lard by fish oil in the diet of mice increases energy expenditure independently of UCP1, decreasing the gain in body weight and adiposity in both protocols. To account for these findings, a model based on the higher mobilization of TAG linked to HUFA for beta-oxidation (relative to less unsaturated moieties) and activation of alternative mechanisms of energy expenditure are proposed to explain the lean phenotype of mice fed with HFDN3. This and other mechanisms of energy expenditure, however, require further investigations.

Introdução: Devido a diversos fatores, recém-nascidos prematuros, em sua maioria, necessitam de nutrição parenteral e uma fonte lipídica que possua um equilíbrio entre os variados tipos de ácidos graxos. SMOFlipid® 20%, uma nova emulsão lipídica pode ser mais adequada para esse equilíbrio. Objetivo: Avaliar o perfil de incorporação de ácidos graxos em eritrócitos de prematuros recebendo essa nova emulsão lipídica, comparada com outra emulsão baseada em óleo de soja. Métodos: Em um ensaio clinico controlado randomizado duplo cego avaliou-se 47 recém-nascidos pré-termo que receberam nutrição parenteral SMOFlipid® 20% (n=25) ou LIPOVENOS® MCT 20% (n=22). Foram avaliados parâmetros laboratoriais, clínicos, demográficos e o perfil de incorporação de ácidos graxos na membrana de eritrócitos. Resultados: Os parâmetros clínicos e demográficos como peso, perímetro cefálico, comprimento, idade gestacional e índice de Apgar não diferiram entre os grupos. Os valores de triglicerídeos e da lipoproteína de muito baixa densidade (VLDL) foram estatisticamente maiores no grupo SMOFLIPID® 20%. Níveis de Aspartato aminotransferase (AST) foram menores em ambos os grupos e os níveis de bilirrubina total e frações não tiveram diferenças. A emulsão SMOFlipid® 20% aumentou os níveis dos ácidos docosa-hexaenoico DHA (C 22:6 w3) e Eicosapentaenoico EPA (C 20:5 w3) na membrana dos eritrócitos. Conclusões: Neste grupo de recém-nascidos pré-termos, essa nova emulsão lipídica, além de mostrar segurança, contribuiu para uma mudança benéfica no perfil de incorporação de ácidos graxos nas membranas celulares, principalmente DHA e EPA / Introduction: Due to several factors, premature newborn infants, in most cases, require parenteral nutrition and a lipid source with balance among the different types of fatty acids. SMOFlipid® 20%, a new lipid emulsion may be more appropriate for this balance. Objectives: To evaluate the profile of fatty acids incorporation in erythrocytes of premature newborn infants receiving this new lipid emulsion compared with an emulsion based on soybean oil. Methods: In a randomized, controlled, double-blind clinical trial, 47 preterm newborn who received parenteral nutrition SMOFlipid® 20% (n=25) or Lipovenos MCT® 20% (n=22) were evaluated. Laboratorial, clinical and demographic parameters and the profile of incorporation of fatty acids in the erythrocyte membrane were evaluated. Results: The clinical and demographic parameters such as weight, head circumference, length, gestational age, and Apgar scores did not differ between the groups. The values of triglycerides and lipoprotein of very low density (VLDL) were statistically higher in the SMOFlipid® 20% group. Levels of aspartate aminotransferase (AST) were lower in both groups and levels of total bilirubin and fractions had no differences. The SMOFlipid® 20% emulsion increased the levels of the docosahexaenoic acid (DHA) and eicosapentaenoic (EPA) acid in the erythrocytes membrane. Conclusions: In this group of preterm newborn infants, this new lipid emulsion, besides showing security, contributed to a beneficial change in the incorporation profile of fatty acids cell membranes, especially DHA and EPA

Doctor of Philosophy / Introduction Cachexia is characterised by a marked weight loss and the presence of anorexia, anaemia, and asthenia. Although cachexia is often associated with the presence and growth of tumour and observed in solid tumours of the upper gastrointestinal tract, its presence is not unique to cancer and is often also present in most chronic, end-stage diseases processes. The loss of body fat, altered lipid metabolism, increase in the resting energy expenditure, and the increased loss of body protein the degree of which is associated with poor survival, are all hallmarks of this detrimental disease. The clinical aspects and consequences of cachexia can simply be summarised as morbidity, debilitating conditions, and mortality. The conditions such as loss of muscle mass, impaired muscle function, fatigue, reduced activity and functional capacity by themselves are enough to severely and significantly affect the patients’ QL. Although different interventional procedures and therapies are available for the treatment of cachexia and its symptoms, effective methods to evaluate their benefits and outcomes have not been tested or investigated. It was, therefore, the aim of this project to use body composition analysis as a clinical tool and evaluate the effectiveness and outcome of interventional and therapeutic procedures in three groups of patients with cancer. Methods Three patient groups were investigated: 1) patients with pancreatic cancer undergoing Whipple’s Procedure, 2) patients with pancreatic cancer undergoing cancer chemotherapy and receiving either EPA or placebo, and 3) patients with malignant mesothelioma undergoing cancer chemotherapy plus thalidomide or thalidomide alone. Body composition analysis techniques were used to assess the changes in TBN, TBF, TBK, and TBW. In addition, the body composition parameters together with clinical measures were also used to determine parameters influencing survival. The malignant mesothelioma patients were randomised into patients who received gemcitabine / cisplatin plus thalidomide and those who received thalidomide alone. The pancreatic cancer patients undergoing chemotherapy were randomised into the group who were receiving EPA and those who were receiving placebo. In addition, these patients were also investigated on the basis of their disease extent where they were separated into two groups of metastatic and locally advanced. Unpaired T-Test and ANOVA were used to determine differences between groups. Kaplan-Meier analysis and Cox’s Regression were used to assess survival in all three patient cohorts. The Whipple’s Procedure patients were separated into those who received a Clear Margin and those who received an Unclear Margin during their resection. Results 1) In the pancreatic cancer patients undergoing Whipple’s Procedure, compared to the base-line, there were highly significant changes in Weight (p=0.006), BMI (p=0.005), and FM (p=0.007) followed by significant changes in %BFat (p=0.016), TBK/Ht (p=0.021), LBM (By TBK) (p=0.023), LBM (Van Loan) (p=0.034), and LBM (Segal) (p=0.038) at the 14 week time-point. At the 26 weeks post-operative time point, the only significant changes were in the FM (p=0.012), %BFat (p=0.003), and BMI (p=0.027) parameters. There was also a deviation between the two groups in their TBN, LBM and TBW content observable in a long-term setting and fat content in the relatively shorter-term. Although the Unclear Margin group had lower body composition values, both groups seem to begin to gradually “equalise” around the 14 weeks post-operative time-point. The survival analysis results for the Whipple’s Procedure patients demonstrated that Margin Status (p=0.001), Fat Mass (p=0.003) and Age (p=0.081) were significant and could influence survival. 2) When the second cohort pancreatic cancer patients undergoing chemotherapy were analysed, they were initially separated according to the extent of their disease The results of the analyses of body composition changes between measurement time-points for the each group separately, suggested that the patients with locally advanced disease maintain their Weight, FM, and TBN but are more likely to have a lower TBW by the end of the four month of chemotherapy. However, the patients with metastatic pancreatic cancer maintain their TBW but are more likely to have a decreased fat compartment and a higher FFM. The QL analysis showed that the metastatic group are performing “worse” than the locally advanced group especially in term of their Dyspnoea, Nausea & Vomiting, and Sexuality. In addition, the Karnofsky score showed that the metastatic group are not performing as well as the locally advanced group. Furthermore, for the metastatic group there was an increase in the patients’ pain with a decline in mood and general performance as well as increase in gastrointestinal symptoms. Pain Card scores also showed a general increase for the metastatic group and a general decrease for the locally advanced group. When the pancreatic cancer patients undergoing chemotherapy were separated according to whether they received EPA or placebo, the results demonstrated that firstly, due to the fact that the patients were well randomised, the two groups commenced the trial with similar and statistically non-significantly different body composition parameters. Secondly, the two groups were also found to be statistically not different at their corresponding measurement time-points. And thirdly, the patients receiving placebo compared to those receiving EPA lost more Weight, and FM but less TBW throughout the trial. The TBK/Ht (p=0.044), TBK (p=0.042), and LBM (By TBK) (p=0.042), however, showed statistically significant differences where in all three parameters the EPA showed an increase compared to the base-line (pre-chemotherapy). Results of the survival analysis demonstrated that the use of EPA in this group of pancreatic cancer patients did not provide any benefit. In fact, as it was shown in the Kaplan-Meier plot, the group of patients receiving the EPA had a “worse” survival than the group receiving the placebo. The QL results showed that placebo group improved in their functional scales, but increased their Altered Bowel Habit scores with an increase in the perception of pain and decrease in relief from pain. The EPA group, however, showed a decrease in the Loss of Appetite, Dyspnoea, Pain, Pancreatic Pain, and Fatigue, and improvements in Role Functioning and Sexuality. 3) Results of the malignant mesothelioma patients demonstrated that both study arms show similar weight changes. In addition, body composition measurements indicated that the gemcitabine / cisplatin chemotherapy plus thalidomide group had a greater TBN loss and a greater TBW gain than the thalidomide-alone group. This loss of TBN and gain in TBW looked to be “concealed” in the weight. The results of the survival analysis carried out on the mesothelioma patient group suggested that haemoglobin levels (p=0.001), Age (p=0.007), and NI (p=0.008) are the parameters that can influence the survival of patients with malignant mesothelioma undergoing chemotherapy. Conclusions 1) The trend in body composition changes in the Whipple’s Procedure group showed that, although both groups may start with non-significantly different body composition, they tended to grow closer around the 14 week point indicating that the Clear Margin group may lose more than Unclear Margin group. The implications of these findings, therefore, were that once the most appropriate surgical procedure is performed, an adjuvant therapy regimen (such as chemotherapy) at around 14 weeks may have the most impact on the patient’s overall treatment outcome. 2) When the pancreatic cancer patients were separated by the extent of their disease, the results lead to the conclusion that the patients with locally advanced disease maintain their Weight, FM, and TBN but are more likely to have a lower TBW by the end of the four month of chemotherapy. However, the patients with metastatic pancreatic cancer maintain their TBW but are more likely to have a decreased fat compartment and a higher FFM. The QL analysis concluded that the results may point to a worsening and/or progressing disease which is consistent with classic metastatic disease aetiology. From the results of the pancreatic cancer patients undergoing cancer chemotherapy it was concluded that the use of EPA in this group of pancreatic cancer patients undergoing cancer chemotherapy with gemcitabine results in a non-significant reduction in weight loss, FM loss, and TBW gain with a statistically significant increase in FFM. The results of the survival analysis was, however, contradictory suggesting that patients receiving EPA may have a worse survival than the placebo group. The QL analysis here concluded that that EPA does improve the QL of this group of pancreatic cancer patients. 3) From the malignant mesothelioma group it was concluded that provided that the overall anti-cancer potential of gemcitabine / cisplatin plus thalidomide is comparable with that of thalidomide-alone, then by looking purely from the body composition angle one may be able to suggest the use of thalidomide alone in the treatment of malignant mesothelioma in this group of patients. From the results of the survival analysis, the fact that the Study Arm parameter did not reach statistical significance could indicate that survival in these patients is not affected by the presence or absence of chemotherapy with gemcitabine and cisplatin. The body composition techniques were used here as a tool to monitor changes in various body composition parameters to assess the outcomes, including survival, of the administration of different therapies and interventional procedures in these three groups of cancer patients. For these purposes, these techniques were demonstrated to be an effective and invaluable tool.

Fish oil is an excellent source of long chain polyunsaturated fatty acids (LC-PUFA), which can reduce the risk of cardiovascular disease in addition to other health benefits. However, the average intake of LC-PUFA in the Western diet is much lower than the recommended levels. Fish oil is prone to oxidative deterioration when exposed to oxygen and thus must be protected in order to be used in food products. Microencapsulation is one possibility that is already applied by the industry to protect fish oil. However, most of the conventional microencapsulation techniques suffer from shortcomings such as harsh processing conditions or the use of numerous chemicals. The main objective of this thesis was to develop a novel spray process to microencapsulate fish oil based on supercritical fluid (SCF) technology using supercritical carbon dioxide (SC-CO2) and CO2-expanded ethanol (CX EtOH). Fundamental physicochemical properties essential for optimal process design were lacking in the literature; therefore, density, interfacial tension (IFT) and viscosity of fish oil in the form of triglycerides and fatty acid ethyl esters were determined at different temperatures and pressures. Fish oil when equilibrated with SC-CO2 at elevated pressure expanded by up to about 40% in volume and increased in density by up to about 5%. Furthermore, IFT of fish oil in contact with SC-CO2 decreased substantially by an order of magnitude with an increase in CO2 pressure. When fish oil was in contact with CX EtOH, IFT decreased to ultra low levels at pressures of less than 10 MPa. Viscosity of fish oil equilibrated with SC-CO2 decreased substantially with pressure but increased with shear rate. Based on the physicochemical properties determined in this research, a novel process to produce micro- and nano-sized particles containing fish oil was developed based on a SCF spray-drying method. Key processing parameters have been evaluated and can be further optimized to improve encapsulation efficiency. Determination of physicochemical properties contributed to the fundamental understanding of the behavior of the fish oil+CO2 system with and without ethanol under high pressure conditions. The new microencapsulation process shows great potential for the delivery of bioactives in various product applications. / Bioresource and Food Engineering