This study evaluated the effect of several heavy metals that are present in flue gases on the algae, focusing on the growth and accumulation of lipids in the algae that can be converted to biodiesel. Concentrations for the heavy metals were calculated based on literature and assumptions. Metals were tested individually first at the highest concentrations that might be present (reference concentrations). The metals and their reference concentrations were: arsenic at 1.56 mg/L, cadmium at 0.3 mg/L, chromium at 2.6 mg/L, cobalt at 0.32 mg/L, copper at 2.62 mg/L, lead at 1.09 mg/L, nickel at 5.08 mg/L, mercury at 0.2 mg/L, selenium at 0.2 mg/L, and zinc at 8.8 mg/L. At these concentrations, most of the metals had a negative effect on the growth and lipid content of the algae. All of the metals were then tested at lower concentrations. At 1/20 the reference concentrations, the metals enhanced growth as well as lipid accumulation in the algae. At higher concentrations there was a negative effect.

No description available.

During mechanical ventilation the diaphragm experiences an extreme case of muscleunloading. In many cases this results in respiratory muscle dysfunctions making it difficult towean the patient off the ventilator. One component in this dysfunction is the accumulation ofintramyocellular lipids (IMCL) in the diaphragm muscle fibres. Using Oil Red O stainingsand confocal microscopy on rat diaphragm sections we have quantified this process. Theresults show a sudden increase in IMCL contents between 18 and 24 hours. No significantdifference between fibre types could be seen.

Vanillin (4-hydroxy-3methoxybenzaldehyde) is one of the most employed aromatic and flavoring additives in food and cosmetic industry. The industrial interest in vanillin could also apply to its biodegradation products. The microbial transformation of vanillin can open the possibility of new products with new areas of application for products related to vanillin. For example, vanillyl alcohol, vanillic acid and ferulic acid are currently used in the pharmaceutical or food industry. Some species reported to biodegrade vanillin into the related products vanillyl alcohol and vanillic acid, are: Brettanomyces anomalus and Saccharomyces cerevisiae. Moreover, certain microorganisms possess the ability to accumulate lipids when cultivated on different carbon sources, opening the possibility of microbial lipid production as another industrial application. The present investigation focuses on the optimization of extraction methods for vanillin biodegradation products, as well as identifying the isolates of a collection of microorganisms originating from the Faroe Islands that are amenable to being cultivated on a lignin-based media. Finally, the potential for microbial lipid accumulation was also studied. Two analytical methods, Thin-Layer Chromatography (TLC) and Gas Chromatography (GC) were employed for characterizing the biodegradation products obtained after 24 hours and 72 hours of culture in growth medium supplemented with 1 mM of vanillin. The results showed that after 24 hours of incubation, the model microorganism, strain FMYD002, had consumed some of the vanillin and transformed it into biodegradation products. TLC retention factors and GC chromatograms revealed that the main biodegradation product after 24 hours - when compared to a standard – is likely to be to vanillyl alcohol. Furthermore, vanillin and its biodegradation products were relatively temperature-stable based on a temperature test of supernatant from a 24-hour culture, however, when the 72-hour culture had been subjected to the highest temperature (60 °C) some spontaneous decomposition occurred. The biodegradation pattern of the 72-hour culture evidenced by TLC revealed two additional biodegradation products, one of which migrates in a similar fashion to vanillic acid. After 72 hours of incubation, the biodegradation product presumed to be vanillyl alcohol was no longer observed. Acidification tests showed that the best route for extraction of the product believed to be vanillyl alcohol is to adjust the extracted sample to a pH of 9. The cultivation test of the isolates in media prepared from different lignin-based residual products showed that 26 out of 60 initial strains grew regardless of the concentration of lignosulfonates and vanillin. Moreover, 17 strains grew in nitrogen-limited medium. Eight of the strains accumulated lipids. A preliminary categorization of isolates based on their colony morphology and capacity of growth on different substrates showed that to some extent, their morphology can predict the ability to grow on lignin- and vanillin-based media. This could help future scientists to easily screen for and select isolates with interesting activity for the ligno-cellulose industry.

Adipogenesis and ectopic lipid accumulation during aging have a great impact on the aging process and the pathogenesis of chronic diseases with age. However, at present, information on the age-related molecular changes in lipid redistribution patterns and their potential nutritional interventions is sparse. We investigated the mechanism underlying age-related lipid redistribution and its modulation using 5-, 17-, and 24-month-old male Fischer 344 rats fed ad libitum (AL) or a 3-week-long CR (40% less than AL) diet. Results revealed that the activities of adipogenic transcription factors were decreased in the white adipose tissue (WAT) of aged AL rats. In contrast, the skeletal muscle of aged AL rats showed increased fat accumulation through decreased carnitine palmitoyltransferase-1 activity, which was blunted by short-term CR. This study suggests an age-related shift in lipid distribution by reducing the adipogenesis of WAT while increasing intramyocellular lipid accumulation, and that CR can modulate age-related adipogenesis and ectopic lipid accumulation.

L’objectif de notre travail était d’étudier les bascules métaboliques chez Yarrowia li-polytica d’un métabolisme purement oxydatif vers l’accumulation de lipides puis à l’excretion d’acide citrique.Le développement d’un procédé D-stat et d’un mode de conduite fed-batch nous a permis, dans un premier temps, de quantifier les ratios N/C caractéristiques pour chacune des bascules étudiées. Nos résultats montrent que les ratios rN/rC critiques aux bascules métaboliques sont de 0,085 molN.Cmol-1 et de 0,018-0,022 molN.Cmol-1 pour l’accumulation de lipides et production de citrate, respectivement.L’analyse systémique des cultures réalisées nous a permis de mettre en évidence des mécanismes de co-régulation de certaines enzymes du métabolisme lipidique ainsi qu’une prépondérance de mécanismes post-transcriptionnels dans l’établissement des bascules étudiées.Enfin, l’utilisation de souches génétiquement modifiées au niveau de l’ATP citrate lyase, la malate déshydrogénase et de la glycérol-3-phosphate déshydogénase a permis d’évaluer l’impact de ces enzymes sur le métabolisme lipidique / This thesis aimed at studying the metabolic shifts in Yarrowia lipolytica from the pure oxidative metabolism to lipid accumulation and citric acid excretion.The development of a D-stat culture and of a monitoring fed-batch strategy allowed us to determine the N/C ratio characteristic for each of metabolic shifts. rN/rC ratio were determined equal to 0,085 molN.Cmol-1 and 0,018-0,022 molN.Cmol-1 for the lipid accumu-lation and the citric acid production, respectively.Systemic analysis of the cultivations showed coregulation phenomena among some enzymes of the lipidic metabolism and post-transcriptional modifications in the onset of the metabolic shifts.Finally, the impact of enzymes (ATP citrate lyase, malate dehydrogenase and gly-cérol-3-phosphate dehydrogenase) on the lipidic metabolism was evaluated through systemic analysis of 3 genetically modified strains

The L-asparaginase (ASNase) obtained from yeasts species has been poorly studied and a new yeast ASNase could be an alternative to minimize the side effect in the treatment of lymphoblastic leukemia. The Antarctic ecosystems have a great potential to obtain novel enzymes produced from psychrophilic and psychrotolerant microorganisms. Yeasts isolated from samples collected in the Antarctic Peninsula by the PROANTAR expedition team were tested for the production of ASNase and L-glutaminase (GLNase). From this screening, the strain Leucosporidium scottii L115 presented the highest ASNase activity (6.24 U g-1 of dried cell weight (dcw)) with a combination of low GLNase activity (0.41 U g-1 dcw). The ASNase belonging to L. scottii L115 (LsASNase) was purified 227 fold with a specific activity of 137.01 U mg-1 at 37 ºC, and with 0.93 U mg-1 for GLNase. Moreover, the maximum activity was observed at pH 7.5 at 55 ºC. The enzyme is a multimer presenting a single band of 54.5 kDa of molecular weight in reduced conditions and 462 kDa by size exclusion chromatography. The LsASNase is a glycosylated enzyme that presented a band lower at 25 kDa when was treated with PGNase F. The enzymatic kinetic reveals an allosteric regulation of the enzyme and the kinetic parameters were determined at 37º C, pH 7.0 as K0.5 = 233 µM, kcat = 54.7 s-1 and nH = 1.52 demonstrating a positive cooperativity by the enzyme and the substrate. The ASNase production by L. scottii L115 was improved by applying DoE for the culture medium development. The PB and CDD designs were used to optimize the ASNase production providing the nutrient values of 6.15 g L-1 of proline, 28.34 g L-1 sucrose, and 15.61 g L-1 of glycerol for a maximal production. The synthetic medium containing the optimized quantities was added with the salts: KCl, 0.52 g L-1; MgSO4.7H2O, 0.52 g L-1; CuNO3.3H2O, 0.001 g L-1; ZnSO4.7H2O, 0.001 g L-1; FeSO4.7H2O, 0.001 g L-1.The optimized medium produces a 23.75 ULh-1 of ASNase in shake flask culture. Furthermore, L. scottii is characterized as an oleaginous yeast that accumulates lipids with a suitable fatty acid profile. The production of ASNase and lipids were scaled up in the 1 L bioreactor to evaluate the initial cell concentration, carbon source, and oxygen transfer rate (kLa).The experiments were performed at 15ºC in the bioreactor BIOSTAT®Q plus (Sartorius Stedim, Germany) in batch mode, using 0.5 L of the optimized medium culture in phosphate buffer 50 mM pH 7.0. The initial cell concentration was evaluated at 1%, 3%, and 5% (v/v). Sucrose and glycerol were tested alone to examine if the combination of both is mandatory to produce ASNase. All these assays were carried in duplicate. The kLa was assessed through a CCD design in the range of 1.42 - 123.0 h-1. The performance in bioreactor showed the productivity of 36.95 ULh-1of ASNase under the optimized conditions (growth temperature 15º C, X0: 5 g L-1, pH 7.0, 48 h, kLa 89-92 h-1). The cultivation of L. scottii L115 at 15ºC in sucrose and glycerol as carbon sources generate an interesting lipid profile, where it presents monounsaturated and polyunsaturated lipids. / A L-asparaginase (ASNase) obtida a partir de espécies de leveduras tem sido pouco estudada e uma nova ASNase de levedura pode ser uma alternativa para minimizar os efeitos adversos no tratamento da leucemia linfoblástica. Os ecossistemas Antárticos têm um grande potencial para obter novas enzimas produzidas a partir de microorganismos psicrofílicos e psicotrolerantes. As leveduras isoladas de amostras coletadas na Península Antártica pela equipe de expedição do PROANTAR foram testadas para a produção de ASNase e L-glutaminase (GLNase). A partir desta triagem, a cepa Leucosporidium scottii L115 apresentou a maior atividade de ASNase (6,24 U g-1 dcw) com uma combinação de baixa atividade de GLNase (0,41 U g-1 dcw). A ASNase pertencente a L. scottii L115 (LsASNase) foi purificada 227 vezes com uma atividade específica de 137,01 U mg-1 a 37 ºC e com 0,93 U mg-1 de GLNase. A atividade máxima foi observada a pH 7,5 a 55 ºC. A enzima é um multímero que apresenta uma banda única de 54,5 kDa de peso molecular em condições redutoras e 462 kDa por cromatografia de exclusão molecular. A LsASNase é uma enzima glicosilada que apresentou uma banda menor a 25 kDa quando tratada com PGNase F. A cinética enzimática revela uma regulação alostérica da enzima e os parâmetros cinéticos foram determinados a 37º C, pH 7,0 como K0,5 = 233 µM, kcat = 54,7 s-1 e nH = 1,52 demonstrando uma cooperatividade positiva pela enzima e o substrato. A produção de ASNase por L. scottii L115 foi melhorada aplicando DoE para o desenvolvimento do meio de cultura. Os desenhos experimentais de PB e CDD forma usados para otimizar a produção de ASNase e forneceram os valores de nutrientes de 6,15 gL-1 de prolina, 28,34 gL-1 de sacarose e 15,61 gL-1 de glicerol para uma produção máxima. O meio sintético contendo as quantidades otimizadas foi adicionado com os sais: : KCl, 0.52 g L-1; MgSO4.7H2O, 0.52 g L-1; CuNO3.3H2O, 0.001 g L-1; ZnSO4.7H2O, 0.001 g L-1; FeSO4.7H2O, 0.001 g L-1.O meio otimizado produz 23.75 ULh-1 de ASNase em cultivo em frasco agitado. Além disso, L. scottii é caracterizada como uma levedura oleaginosa que acumula lipídios com um perfil adequado de ácidos graxos. A produção de ASNase e lipídios foi ampliada no biorreator de 1 L para avaliar a concentração celular inicial, fonte de carbono e taxa de transferência de oxigênio (kLa). Os experimentos foram realizados a 15ºC no biorreator BIOSTAT®Q plus (Sartorius Stedim) em modo batelada, utilizando 0,5 L da cultura de meio otimizado em tampão fosfato 50 mM pH 7,0. A concentração celular inicial foi avaliada em 1%, 3% e 5% (v / v). Sacarose e glicerol foram testados isoladamente para examinar se a combinação de ambos é obrigatória para produzir ASNase. Todos esses ensaios foram realizados em duplicado. O kLa foi avaliado através de um planejamento CCD na faixa de 1,42-123,0 h-1. O desempenho no biorreator mostrou a produtividade de 36,95 ULh-1 de ASNase sob condições otimizadas (temperatura de crescimento 15º C, X0: 5 g L-1, pH 7,0, 48 h, kLa 89-92 h-1). O cultivo de L. scottii L115 a 15ºC em sacarose e glicerol como fontes de carbono gera um perfil lipídico interessante, onde apresenta lipídios monoinsaturados e poliinsaturados.

The L-asparaginase (ASNase) obtained from yeasts species has been poorly studied and a new yeast ASNase could be an alternative to minimize the side effect in the treatment of lymphoblastic leukemia. The Antarctic ecosystems have a great potential to obtain novel enzymes produced from psychrophilic and psychrotolerant microorganisms. Yeasts isolated from samples collected in the Antarctic Peninsula by the PROANTAR expedition team were tested for the production of ASNase and L-glutaminase (GLNase). From this screening, the strain Leucosporidium scottii L115 presented the highest ASNase activity (6.24 U g-1 of dried cell weight (dcw)) with a combination of low GLNase activity (0.41 U g-1 dcw). The ASNase belonging to L. scottii L115 (LsASNase) was purified 227 fold with a specific activity of 137.01 U mg-1 at 37 ºC, and with 0.93 U mg-1 for GLNase. Moreover, the maximum activity was observed at pH 7.5 at 55 ºC. The enzyme is a multimer presenting a single band of 54.5 kDa of molecular weight in reduced conditions and 462 kDa by size exclusion chromatography. The LsASNase is a glycosylated enzyme that presented a band lower at 25 kDa when was treated with PGNase F. The enzymatic kinetic reveals an allosteric regulation of the enzyme and the kinetic parameters were determined at 37º C, pH 7.0 as K0.5 = 233 µM, kcat = 54.7 s-1 and nH = 1.52 demonstrating a positive cooperativity by the enzyme and the substrate. The ASNase production by L. scottii L115 was improved by applying DoE for the culture medium development. The PB and CDD designs were used to optimize the ASNase production providing the nutrient values of 6.15 g L-1 of proline, 28.34 g L-1 sucrose, and 15.61 g L-1 of glycerol for a maximal production. The synthetic medium containing the optimized quantities was added with the salts: KCl, 0.52 g L-1; MgSO4.7H2O, 0.52 g L-1; CuNO3.3H2O, 0.001 g L-1; ZnSO4.7H2O, 0.001 g L-1; FeSO4.7H2O, 0.001 g L-1.The optimized medium produces a 23.75 ULh-1 of ASNase in shake flask culture. Furthermore, L. scottii is characterized as an oleaginous yeast that accumulates lipids with a suitable fatty acid profile. The production of ASNase and lipids were scaled up in the 1 L bioreactor to evaluate the initial cell concentration, carbon source, and oxygen transfer rate (kLa).The experiments were performed at 15ºC in the bioreactor BIOSTAT®Q plus (Sartorius Stedim, Germany) in batch mode, using 0.5 L of the optimized medium culture in phosphate buffer 50 mM pH 7.0. The initial cell concentration was evaluated at 1%, 3%, and 5% (v/v). Sucrose and glycerol were tested alone to examine if the combination of both is mandatory to produce ASNase. All these assays were carried in duplicate. The kLa was assessed through a CCD design in the range of 1.42 - 123.0 h-1. The performance in bioreactor showed the productivity of 36.95 ULh-1of ASNase under the optimized conditions (growth temperature 15º C, X0: 5 g L-1, pH 7.0, 48 h, kLa 89-92 h-1). The cultivation of L. scottii L115 at 15ºC in sucrose and glycerol as carbon sources generate an interesting lipid profile, where it presents monounsaturated and polyunsaturated lipids. / A L-asparaginase (ASNase) obtida a partir de espécies de leveduras tem sido pouco estudada e uma nova ASNase de levedura pode ser uma alternativa para minimizar os efeitos adversos no tratamento da leucemia linfoblástica. Os ecossistemas Antárticos têm um grande potencial para obter novas enzimas produzidas a partir de microorganismos psicrofílicos e psicotrolerantes. As leveduras isoladas de amostras coletadas na Península Antártica pela equipe de expedição do PROANTAR foram testadas para a produção de ASNase e L-glutaminase (GLNase). A partir desta triagem, a cepa Leucosporidium scottii L115 apresentou a maior atividade de ASNase (6,24 U g-1 dcw) com uma combinação de baixa atividade de GLNase (0,41 U g-1 dcw). A ASNase pertencente a L. scottii L115 (LsASNase) foi purificada 227 vezes com uma atividade específica de 137,01 U mg-1 a 37 ºC e com 0,93 U mg-1 de GLNase. A atividade máxima foi observada a pH 7,5 a 55 ºC. A enzima é um multímero que apresenta uma banda única de 54,5 kDa de peso molecular em condições redutoras e 462 kDa por cromatografia de exclusão molecular. A LsASNase é uma enzima glicosilada que apresentou uma banda menor a 25 kDa quando tratada com PGNase F. A cinética enzimática revela uma regulação alostérica da enzima e os parâmetros cinéticos foram determinados a 37º C, pH 7,0 como K0,5 = 233 µM, kcat = 54,7 s-1 e nH = 1,52 demonstrando uma cooperatividade positiva pela enzima e o substrato. A produção de ASNase por L. scottii L115 foi melhorada aplicando DoE para o desenvolvimento do meio de cultura. Os desenhos experimentais de PB e CDD forma usados para otimizar a produção de ASNase e forneceram os valores de nutrientes de 6,15 gL-1 de prolina, 28,34 gL-1 de sacarose e 15,61 gL-1 de glicerol para uma produção máxima. O meio sintético contendo as quantidades otimizadas foi adicionado com os sais: : KCl, 0.52 g L-1; MgSO4.7H2O, 0.52 g L-1; CuNO3.3H2O, 0.001 g L-1; ZnSO4.7H2O, 0.001 g L-1; FeSO4.7H2O, 0.001 g L-1.O meio otimizado produz 23.75 ULh-1 de ASNase em cultivo em frasco agitado. Além disso, L. scottii é caracterizada como uma levedura oleaginosa que acumula lipídios com um perfil adequado de ácidos graxos. A produção de ASNase e lipídios foi ampliada no biorreator de 1 L para avaliar a concentração celular inicial, fonte de carbono e taxa de transferência de oxigênio (kLa). Os experimentos foram realizados a 15ºC no biorreator BIOSTAT®Q plus (Sartorius Stedim) em modo batelada, utilizando 0,5 L da cultura de meio otimizado em tampão fosfato 50 mM pH 7,0. A concentração celular inicial foi avaliada em 1%, 3% e 5% (v / v). Sacarose e glicerol foram testados isoladamente para examinar se a combinação de ambos é obrigatória para produzir ASNase. Todos esses ensaios foram realizados em duplicado. O kLa foi avaliado através de um planejamento CCD na faixa de 1,42-123,0 h-1. O desempenho no biorreator mostrou a produtividade de 36,95 ULh-1 de ASNase sob condições otimizadas (temperatura de crescimento 15º C, X0: 5 g L-1, pH 7,0, 48 h, kLa 89-92 h-1). O cultivo de L. scottii L115 a 15ºC em sacarose e glicerol como fontes de carbono gera um perfil lipídico interessante, onde apresenta lipídios monoinsaturados e poliinsaturados.

Made available in DSpace on 2016-08-19T18:16:05Z (GMT). No. of bitstreams: 1 Dissertacao Joelma.pdf: 599807 bytes, checksum: 496d32d46e118e53ae391f662bfa6dbd (MD5) Previous issue date: 2012-10-29 / FUNDAÇÃO DE AMPARO À PESQUISA E AO DESENVOLVIMENTO CIENTIFICO E TECNOLÓGICO DO MARANHÃO / The polycystic ovary syndrome (PCOS) is considered the most common endocrine disease during the woman's reproductive life, with prevalence ranging from 5 to 10% of women of reproductive age and is characterized by chronic anovulation and hyperandrogenism, showing complex multifactorial pathogenesis. Objective: To determine the cutoff the lipid accumulation product in women with polycystic ovary syndrome. Methods: Cross-sectional study with 78 women between 18 and 42 years diagnosed with polycystic ovary syndrome according to the Rotterdam criteria directed to nutritional evaluation at the Maternal and Child Unit of the University Hospital UFMA. The interest variables were recorded in protocol form: socio-demographic, behavioral, gynecological history, personal and family history of diseases, anthropometric data (weight, height, body mass index and waist circumference), laboratory tests, imaging exams and blood pressure values. The product of lipid accumulation was calculated by the formula described by Kahn. Regarding the analysis of data normality of quantitative variables was analyzed by the Shapiro Wilk; to compare the means of the variables we used the t Student test. To check the correlation between the lipid product accumulation and cardiovascular risk markers was applied Linear Correlation coefficient (r) test. The lipid product accumulation was analyzed according to the Receiver Operating Characteristic Curve, being discriminated values of high sensitivity and specificity simultaneously. The significance level for all tests was 5%. Results: Using the Receiver Operating Characteristic curve to determine the best cutoff of predicted LAP index risk for cardiovascular disease, it was noted that the value above 39.32 cm.mmol/L representing the area under the 0.8845 of the curve. Every women who had lipid product accumulation product value above the cutoff defined also showed the highest changes in mean of risk markers analyzed of cardiovascular diseases, a statistically significant difference. Regarding the analysis of correlation between the product of lipid accumulation above the cutoff defined and risk markers for cardiovascular diseases, there was a significant correlation. Conclusion: These results demonstrate that cutoff values ≥ 39.32 cm.mmol/L of LAP index seems to indicate the increased risk for CVD and should be used as a screening tool and research for its ease of measurement and interpretation, as well as its low cost and may even have its applicability in primary health care. / A síndrome dos ovários policísticos (SOP) é considerada a endocrinopatia mais comum durante a vida reprodutiva da mulher, com prevalência que varia entre 5 a 10% das mulheres em idade fértil sendo caracterizada por anovulação crônica e hiperandrogenismo, apresentando fisiopatogenia complexa de caráter multifatorial. Objetivo: Determinar o ponto de corte do produto da acumulação lipídica em mulheres com síndrome dos ovários policísticos. Metodologia: Estudo transversal realizado com 78 mulheres entre 18 e 42 anos atendidas no Hospital Universitário Unidade Materno-Infantil da Universidade Federal do Maranhão com o diagnóstico de síndrome dos ovários policísticos de acordo com os critérios de Rotterdam. As variáveis de interesse foram registradas em ficha-protocolo com: dados sócio-demográficos, comportamentais, história ginecológica, antecedentes pessoais e familiares de patologias, dados antropométricos (peso, altura, índice de massa corporal e circunferência da cintura), exames laboratoriais, exame de imagem e valores de pressão arterial. O produto da acumulação lipídica foi calculado pela fórmula descrita por Kahn. Com relação à análise de dados a normalidade das variáveis quantitativas foi analisada pelo teste Shapiro Wilk, para comparação das médias das variáveis utilizou-se o Teste t de Student. Na verificação de Correlação entre o produto da acumulação lipídica e os marcadores de risco cardiovascular foi aplicado o teste de Correlação Linear de Pearson (r). O produto da acumulação lipídica foi submetido à análise segundo a Curva Receiver Operating Characteristic, sendo discriminados os valores de maior sensibilidade e especificidade, simultaneamente. O nível de significância para todos os testes foi de 5%. Resultados: Utilizando-se a Curva Receiver Operating Characteristic para determinar o melhor ponto de corte do produto da acumulação lipídica preditivo de risco para doença cardiovascular, notou-se que o valor acima de 39,32 cm.mmol/L, representou a área sob a curva de 0,8845. Todas as mulheres que apresentaram o valor do produto da acumulação lipídica acima do ponto de corte definido, também apresentaram as maiores alterações nas médias dos marcadores de risco de doença cardiovascular analisados, diferença estatisticamente significativa. No que concerne à análise de correlação entre o produto da acumulação lipídica acima do ponto de corte definido e os marcadores de risco para doenças cardiovasculares, houve uma correlação significativa. Conclusão: Estes resultados demonstram que valores de ponto de corte ≥ 39,32 cm.mmol/L do produto da acumulação lipídica parecem apontar risco aumentado à doença cardiovascular e pode ser utilizado como ferramenta de triagem e investigação pela sua facilidade de mensuração e interpretação, além do baixo custo, podendo ter, inclusive, sua aplicabilidade na atenção primária em saúde.

Le but de ce travail de doctorat est de contribuer à l'optimisation de l'accumulation de lipides par les levures oléagineuses, et plus particulièrement par la levure Yarrowia lipolytica à partir du glucose, avec une stratégie d’optimisation dynamique à partir d’une commande basée sur un modèle. L’étude bibliographique permet de faire le bilan des connaissances antérieures pour identifier les différentes méthodologies existantes pour l’optimisation des procédés en structurant trois parties principales: la modélisation, la commande, et le suivi des procédés. Dans ce contexte, cinq modèles ont été proposés pour décrire l'accumulation de lipides. Le premier est un modèle non structuré basé sur des cinétiques de Monod et d’inhibition. Le deuxième s’appuie sur le modèle de Droop (quota) précédemment utilisé pour décrire l’accumulation de lipides dans les microalgues. Les trois derniers sont des modèles métaboliques dynamiques qui combinent les cinétiques avec un réseau métabolique réduit, obtenu à partir des modes élémentaires. Les cinq modèles ont été calibrés et validés en utilisant plusieurs jeux des données expérimentales. Néanmoins, un des avantages des modèles métaboliques dynamiques présentés est la possibilité de décrire les basculements métaboliques. Deux stratégies de commande multi-objective visant à maximiser la productivité des lipides et la fraction en teneur lipidique ont été proposées. Dans la première, les deux objectifs ont été pondérés par le calcul statique des fronts de Pareto, et intégrés à la stratégie de commande avec un modèle dynamique métabolique. La deuxième stratégie est basée sur des fonctions linéaires par morceaux en intégrant le modèle quota. Les simulations de la commande montrent la possibilité d’atteindre des teneurs en lipides entre 0,21 – 0,26 gLIP.gX-1 et productivités entre 0,78 – 1,02 g.(L-h)-1 en diminuant le temps de la culture à 20 h. Des capteurs logiciels ont été proposés afin de pallier le manque de capteurs en ligne en corrélant des mesures en ligne (i.e. pO2 et la base ajoutée pour le pH) par des algorithmes de types machines à vecteurs supports. La validation expérimentale des stratégies de commande est la principale perspective de ce travail. / This PhD thesis aims at optimizing lipid accumulation by oleaginous yeast, and most particularly by the yeast Yarrowia lipolytica from glucose. This optimization is addressed from a mathemantical point of view based on automatic control laws, where model-based control strategies are proposed. The bibliographic review compiles and evaluates previous works to identify the different existing methodologies to attain the optimization, which is divided in three main axes: modeling, control strategies, and monitoring. In this context, five different models are proposed to describe lipid accumulation. The first model is based on Monod and inhibition kinetics (unstructured), and the second on the Droop quota model (quota) previously used for microalgae. The last three are dynamic metabolic models that combine kinetics with metabolic models based on the stoichiometry of metabolism. These three models used a reduced metabolic network decomposed into elementary flux modes. The five models were successfully calibrated and validated with different experimental data. Nonetheless, the dynamic metabolic models presented highlighting features such as the description of metabolic shifts. Two approaches of multi-objective control strategies aiming at maximizing lipid productivity and lipid content fraction were proposed. In the first, the two objectives were weighted by static calculation of Pareto fronts, and integrated to the control strategy by dynamic optimization algorithms with a dynamic metabolic model. The second strategy used a constant weighed objective function solved by piecewise linear functions by integrating the quota model. The simulation results of the optimization attained lipid contents between 0.21 – 0.26 gLIP.gX-1 and productivities between 0.78 – 1.02 g.(L-h)-1 shortening the culture time to 20 h. Soft-sensors were developed by correlating on-line measurements (i.e. pO2 and the added base for pH) through support vector machines in order to overcome the lack of measurements. The perspective is to experimentally validate the control strategies.