Introdução: Durante a síndrome da resposta inflamatória sistêmica acontecem importantes alterações no metabolismo lipídico. Estas alterações são descritas nos pacientes adultos com sepse grave, porém o perfil lipídico no paciente pediátrico gravemente doente é pouco conhecido. Além disso, nos pacientes gravemente doentes baixas concentrações de colesterol foram associadas a maior gravidade da doença e aumento na mortalidade. Objetivos: Avaliar a relação entre a intensidade da reposta inflamatória e alterações no perfil lipídico em crianças e adolescentes gravemente doentes à admissão na UTI e se estas alterações se atenuam à medida que há resolução do processo inflamatório. Métodos: Analisamos o perfil lipídico de 40 pacientes com SIRS/sepse admitidos numa UTI Pediátrica de nível I. A Proteína C Reativa (PCR) foi utilizada para caracterizar resposta inflamatória. Mensuramos os níveis séricos de triglicerídeos (TG), colesterol total (CT), lipoproteína de alta densidade (HDL), lipoproteína de baixa densidade (LDL) e apolipoproteínas à admissão e no sétimo dia de internação. Utilizamos um grupo controle de 42 pacientes pediátricos avaliados no pronto socorro que não apresentavam sinais de sepse. Foi utilizado o Pediatric Risk of Mortality Score nos pacientes admitidos na UTI e realizada avaliação nutricional nos dois grupos. Resultados: As concentrações de PCR apresentaram-se bastante elevadas no 1º dia do estudo e tiveram uma redução significativa durante a evolução. Os pacientes internados na UTI tiveram níveis significativamente mais baixos de CT, HDL, LDL bem como concentrações mais altas de TG em comparação ao grupo controle. Houve um aumento significativo nos níveis de CT, HDL, LDL e apolipoproteínas entre o primeiro e sétimo dias de estudo. Não houve relação entre a classificação nutricional e as concentrações de lipoproteínas. Conclusão: Durante a resposta inflamatória encontramos níveis séricos mais baixos de lipídeos e apolipoproteínas com associação inversa em relação às concentrações de PCR. À medida que houve resolução da resposta inflamatória os níveis de CT, HDL, LDL e apolipoproteínas aumentaram mostrando relação direta entre as alterações no perfil lipídico e a inflamação. As alterações no perfil lipídico não se associaram ao estado nutricional / Introduction: During the course of systemic inflammatory response syndrome, there are important changes in lipid metabolism. These changes are described in adult patients with severe sepsis, but little is known about lipid profile in critically ill pediatric patients. Furthermore, in critically ill patients low cholesterol levels were shown to be correlated with the severity of disease and associated with higher mortality rates. Purpose: To evaluate the relationship among the intensity of the inflammatory response and changes in lipid profile in critically ill children and adolescents on admission to the PICU and whether these changes are attenuated as there is resolution of the inflammatory process. Materials and Methods: We analyzed the serum lipid in 40 patients with SIRS/sepsis admitted to the level I pediatric ICU. The C-reactive protein (CRP) was used to characterize the inflammatory response. We measured serum levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and apolipoprotein on admission and on the seventh day of hospitalization. We used a control group of 42 pediatric patients seen in emergency department without sepsis. Severity of disease was evaluated with Pediatric Risk of mortality score (PRISM) on admission and nutrition classification was performed in all patients. Results: CRP concentrations were very high on the first day of the study and had a significant reduction during evolution. On admission to the PICU, patients had significantly lower levels of TC, HDL, LDL as well as higher concentrations of TG in comparison with control group. There was a significant increase in the TC, HDL, LDL and apolipoprotein levels between the first and seventh days of the study. There was no relationship between the nutritional classification and lipoproteins levels. Conclusions: During the systemic inflammatory response we found lower serum levels of lipids and apolipoproteins with negative correlation in relation to CRP. As improvement in the inflammatory response, the levels of CT, HDL, LDL and apolipoprotein increased showing a direct relationship among changes in lipid profile and inflammation. Changes in lipid profile were not associated with nutritional status

A Arginina (Arg) regula a secreção de GH e insulina, e é o único precursor biológico do NO. Previamente demonstramos que animais tratados cronicamente com Arg (35mg/dia) desenvolvem resistência à insulina (RI), e o presente estudo investigou as suas bases moleculares. A RI baseou-se na redução da atividade e/ou expressão do IRS 1/2 e Akt, e do conteúdo de GLUT4; sendo o GH crucial na gênese desses efeitos. Doses mais elevadas de Arg (70mg/dia/30 dias), a maior geração de NO e a melhora do fluxo sangüíneo reverteram este quadro. Experimentos com células musculares demonstraram que a Arg estimula o metabolismo de glicose e lipídios, via NO/c-GMP. Esses achados indicam que a Arg pode ser benéfica para o tratamento de distúrbios metabólicos, como obesidade e DM2; e que ao estimular a secreção de GH, em doses adequadas, seria eficaz na terapia de distúrbios da secreção deste hormônio. Todavia, estudos adicionais são necessários para investigar a melhor dose e os efeitos crônicos in vivo da Arg, uma vez que o GH em excesso apresenta um efeito diabetogênico importante. / Arginine (Arg) regulates the secretion of GH and insulin, and it is the main biological precursor of NO. We have previously shown that animals chronically-treated with Arg (35 mg/day) developed insulin resistance (IR), and this study investigated its molecular basis. The RI relies on the reduction of the activity and/or expression of IRS 1/2 and Akt, and of the GLUT4 content; and GH has a crucial role in the genesis of these effects. Higher doses of Arg (70 mg/dia/30 days), the increased NO generation and the improvement of the blood flow reversed the RI. Experiments with muscle cells showed that Arg stimulates glucose and lipids metabolism, via NO/c-GMP activation. These findings indicate that Arg may be beneficial for the treatment of metabolic disorders, such as obesity and T2DM, and by stimulating GH secretion, Arg can, in appropriate doses, be effective for the therapy of GH secretion disorders. However, further studies are needed to investigate the best dose and the chronic effects of Arg in vivo, since that GH in excess is potentially diabetogenic.

Numerous studies have investigated how bulk lipid metabolism is influenced in obesity and in particular how the composition of triglycerides found in the cytosol change with increased adipocyte expansion. However, in part reflecting the analytical challenge the composition of cell membranes, and in particular glycerophospholipids, an important membrane component, have been seldom investigated. Cell membrane components contribute to a variety of cellular processes including maintaining organelle functionality, providing an optimized environment for numerous proteins and providing important pools for metabolites, such as choline for one-carbon metabolism and S-adenosylmethionine for DNA methylation. Here, I have conducted a comprehensive lipidomic and transcriptomic study of white adipose tissue in mice that become obese either through genetic modification (ob/ob genotype), diet (high-fat diet) or a combination of the two across the life course. Specifically, I demonstrated that the changes in triglyceride metabolism that dominate the overall lipid composition of white adipose tissue were distinct from the compositional changes of glycerophospholipids. These latter lipids became more unsaturated to maintain the fluidity and normal function of the membrane in the initiation of obesity but then turned saturated after long-term administration of HFD and aging. This suggests that while triglycerides within the adipose tissue may be a relatively inert store of lipids, the compositional changes occur in cell membranes with more far-reaching functional consequences in both obesity and aging. The two-phase change of phospholipids can be correlated well with transcriptional and one-carbon metabolic changes within the adipocytes. The transcriptomic study demonstrated that the lipid metabolic pathways regulated by the peroxisome, AMPK, insulin and PPARγ signaling were activated in the initiation of obesity but inhibited in the adipose tissue of old ob/ob mice along with up-regulated inflammation pathways. The brown and white adipose tissue of PPARα-knock-out mice were also studied by lipidomic tools to get a deeper understanding of the effect of the peroxisome and PPAR system on adipose tissue and lipid metabolism during obesity. Most of the lipids were increased and became more saturated and shorter in adipose tissues of PPARα null mice, which is in good accordance with the results of the former animal study. In conclusion, my work using different rodent models and multi-omics techniques demonstrated a protective metabolic mechanism activated in the initiation but impaired at the end of the processes of obesity and aging, which could be an explanation of the similarity of obesity and aging in terms of high incidence of the metabolic syndrome and related diseases.

L’objectif de la thèse était d'identifier s’il existait des différences d’utilisation digestive et métabolique des glucides alimentaires entre deux lignes de truite sélectionnées pour leur teneur divergente en lipides intramusculaires: la lignée maigre (L) à faible taux de lipides dans le muscle et la lignée grasse (F) à teneur élevée de lipides musculaires. Dans ce but les deux lignées ont été nourries avec deux aliments, un contenant des glucides alimentaires (20% d’amidon), l’autre ne contenant pas. Chez les deux lignées, la présence d’amidon dans les régimes n’a pas eu d’effets sur la croissance, a été associée à une épargne protéique, et a provoqué une hyperglycémie postprandiale modérée, en induisant les acteurs impliqués dans la signalisation cellulaire (TOR/AMPK). Aucune différence entre les deux lignées n’a été observée pour la digestion de l'amidon, le niveau d’expression des gènes codant les transporteurs de glucose dans l’intestin, la glycémie postprandiale et l'utilisation périphérique du glucose (muscle et tissu adipeux). Par contre, la lignée F se caractérise par une croissance et une efficacité alimentaire plus faibles, des capacités plus élevées de stockage du glucose sous forme de glycogène hépatiques et de lipogenèse (sans impact sur l’utilisation des glucides) et un métabolisme lipidique spécifique (plus faible catabolisme des acides gras, plus fortes capacités à synthétiser des chylomicrons et à bio-convertir des acides gras). Dans une seconde étude, le remplacement de l'huile de poisson de l’aliment par un mélange d'huiles végétales a supprimé la plupart des différences moléculaires observées précédemment entre les deux génotypes. Toutefois, l’apport de glucides alimentaires a alors entrainé des modifications métaboliques au niveau intestinal et hépatique avec, par exemple, l’induction des capacités moléculaires de bioconversions des acides gras. Globalement, nos données ont donc démontré qu’il existait des différences métaboliques importantes entre les deux lignées mais que cela n’aboutissait pas à une meilleure utilisation des glucides alimentaires. En outre, nos travaux soulignent l'importance de la composition des aliments dans les réponses' des différents génotypes de poissons. / The aim of the thesis was to characterise the differences in digestive and metabolic utilisation of dietary carbohydrates between two lines of rainbow trout divergently selected for muscle fat content (Fat-F and Lean-L), when fed diets with (20%) or without gelatinised starch. In both lines, starch intake did not adversely affect growth, resulted in a moderate postprandial hyperglycemia, enhanced protein/lipid retention and a distinct intracellular signalling pattern in the liver involving the energy sensor AMPK and nutrient sensor TOR-S6. No difference between the two lines was observed for the apparent digestibility of starch, the mRNA levels of genes encoding glucose transporters in the intestine, regulation of postprandial glycemia and utilisation of glucose in the peripheral tissues (muscle and adipose tissue). However when compared to the L line, the F line was characterised by lower growth and feed efficiency; better capacity to store excess glucose as indicated by higher glycogen levels and mRNA levels of lipogenic markers in the liver (with no impact on glucose homeostasis); and a specific lipid metabolism (a greater potential to synthesise chylomicrons and to bioconvert fatty acids, coupled with a lower potential to oxidise fatty acids). In a separate study, replacement of fish oil in the diet with a blend of vegetable oils was found to suppress most of the molecular differences previously observed between the two genotypes. Starch intake under the vegetable oil diet regime led to different metabolic changes in the intestine and liver, for example, elicited a higher transcriptional response of key desaturase and elongase enzymes in both lines. Overall, our data demonstrated the existence of significant metabolic differences between the two trout lines, but it did not lead to better utilisation of dietary carbohydrates. In addition, our work highlights the importance of diet composition in the growth and metabolic response of different genotypes of fish.

A influência da obesidade sobre o fígado e a função hepática é tema ainda pouco estudado e discutido, principalmente no Brasil. O crescente aumento da população obesa de maneira global alerta sobre esse grave problema, que hoje em dia, se torna de saúde pública. Amplia-se, cada vez mais, o número de pessoas e a faixa etária atingida. A doença hepática não alcoólica é uma condição clínico-patológica comum caracterizada por depósitos de lipídios em hepatócitos no parênquima hepático. Um espectro de danos ocorrem no parênquima, desde uma simples esteatose macrogoticular podendo evoluir para esteato-hepatite, fibrose e até cirrose. Os casos de esteatose hepática não alcoólica (EHNA) que progridem para cirrose tem sido reconhecidos como a maior causa de morbidade e mortalidade com potencial para progredir para falência hepática. Apesar de haver um aumento na prevalência da doença hepática não alcoólica, os critérios para seu diagnóstico continuam pobremente definidos. A utilização da espectroscopia de prótons na ressonância magnética auxilia na quantificação do conteúdo lipídico hepático e na musculatura da perna (tibial anterior e sóleo), embora venha sendo utilizada apenas em pesquisas. Tivemos como objetivos o estudo do metabolismo lipídico de humanos xii obesos por espectroscopia por ressonância magnética, correlacionando com dados laboratoriais e de biópsias hepáticas. Neste estudo observacional transversal e prospectivo realizado em obesos, que foram submetidos a cirurgia redutora gástrica pela técnica de Capella no Hospital Prof. Edmundo Vasconcelos em São Paulo, foram incluídos 27 pacientes analisados no pré e pós-operatório para descrição dos dados. Foi constatada uma razão masculino/feminino geral de 8 :19 e a faixa etária entre 24 e 55 anos. Os índices de massa corpórea (IMC) eram sempre superiores a 40 Kg/m² para inclusão cirúrgica. Os pacientes obesos que no pré-operatório apresentavam esteatose hepática observada na ressonância magnética e esteatose e/ou esteato-hepatite na biópsia hepática evoluíram com melhora ou resolução no pós-operatório. Em conclusão, em pacientes obesos o grau de esteatose hepática pode ser analisado qualitativa e quantitativamente através da ressonância magnética com espectroscopia assim como, o controle pós tratamento cirúrgico evitando-se a utilização de métodos invasivos, entre eles a biópsia hepática. / The obesity influence on the liver and the hepatic function are themes that are not so discussed or studied, especially in Brazil. The world-wide increasing number of obese people calls the attention to this serious problem, that nowadays, became a public health problem. The number of people and the age of the people who suffer from it is increasing each day more. The non-alcoholic hepatic disease is a common pathological clinic condition caractherized by lipid deposits in hemocytes in the hepatic parenchyma. There are some injuries in the parenchyma, since a single steatosy macrogoticular to a steatohepatitis, a fibrosis and even a cirrhosis (Sass et al., 2005). The non-alcoholic steatosy hepatic (NASH) cases which lead to a cirrhosis have been known as the main causes of death with possibilities to evolute to a hepatic fail. Besides there is an increasing in the non-alcoholic hepatic disease, the means for its diagnosis still remain poorly defined. The protons spectroscopy use, in the magnetic resonance, helps on the lipidic hepatic contents numbers, although it has been used only for researches. We had as a goal the lipid metabolism study of obese human beings, related to the laboratorials data and the hepatic biopsy. On this study, where we observed obese people that were submitted to a gastric reducing surgery by the Capella techinic in the hospital Prof. Edmundo Vasconcelos in São Paulo, were included 27 pacients analyzed on the before and after operation for the datas description. It was noted a male/female general reason 9: 18 and the ages between 24 and 55 years old. The body mass indexes (IMC) were always over 40 Kg/m² to be included in a surgery. The obese patients who presented steatosy hepatic before operatory observed on the magnetic resonance and steatosy and/or steatohepatitis during the hepatic biosy went better on the pos-operatory. Finally, in obese patients the xiv steatosy hepatic degree can be analysed on its qualitativy and quantitativy through the magnetic resonance with spectroscopy, and so the cirurgical pos- treatment control, avoiding the use of invasive methods, among them the hepatic biopsy.

Introdução: Durante a síndrome da resposta inflamatória sistêmica acontecem importantes alterações no metabolismo lipídico. Estas alterações são descritas nos pacientes adultos com sepse grave, porém o perfil lipídico no paciente pediátrico gravemente doente é pouco conhecido. Além disso, nos pacientes gravemente doentes baixas concentrações de colesterol foram associadas a maior gravidade da doença e aumento na mortalidade. Objetivos: Avaliar a relação entre a intensidade da reposta inflamatória e alterações no perfil lipídico em crianças e adolescentes gravemente doentes à admissão na UTI e se estas alterações se atenuam à medida que há resolução do processo inflamatório. Métodos: Analisamos o perfil lipídico de 40 pacientes com SIRS/sepse admitidos numa UTI Pediátrica de nível I. A Proteína C Reativa (PCR) foi utilizada para caracterizar resposta inflamatória. Mensuramos os níveis séricos de triglicerídeos (TG), colesterol total (CT), lipoproteína de alta densidade (HDL), lipoproteína de baixa densidade (LDL) e apolipoproteínas à admissão e no sétimo dia de internação. Utilizamos um grupo controle de 42 pacientes pediátricos avaliados no pronto socorro que não apresentavam sinais de sepse. Foi utilizado o Pediatric Risk of Mortality Score nos pacientes admitidos na UTI e realizada avaliação nutricional nos dois grupos. Resultados: As concentrações de PCR apresentaram-se bastante elevadas no 1º dia do estudo e tiveram uma redução significativa durante a evolução. Os pacientes internados na UTI tiveram níveis significativamente mais baixos de CT, HDL, LDL bem como concentrações mais altas de TG em comparação ao grupo controle. Houve um aumento significativo nos níveis de CT, HDL, LDL e apolipoproteínas entre o primeiro e sétimo dias de estudo. Não houve relação entre a classificação nutricional e as concentrações de lipoproteínas. Conclusão: Durante a resposta inflamatória encontramos níveis séricos mais baixos de lipídeos e apolipoproteínas com associação inversa em relação às concentrações de PCR. À medida que houve resolução da resposta inflamatória os níveis de CT, HDL, LDL e apolipoproteínas aumentaram mostrando relação direta entre as alterações no perfil lipídico e a inflamação. As alterações no perfil lipídico não se associaram ao estado nutricional / Introduction: During the course of systemic inflammatory response syndrome, there are important changes in lipid metabolism. These changes are described in adult patients with severe sepsis, but little is known about lipid profile in critically ill pediatric patients. Furthermore, in critically ill patients low cholesterol levels were shown to be correlated with the severity of disease and associated with higher mortality rates. Purpose: To evaluate the relationship among the intensity of the inflammatory response and changes in lipid profile in critically ill children and adolescents on admission to the PICU and whether these changes are attenuated as there is resolution of the inflammatory process. Materials and Methods: We analyzed the serum lipid in 40 patients with SIRS/sepsis admitted to the level I pediatric ICU. The C-reactive protein (CRP) was used to characterize the inflammatory response. We measured serum levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL) and apolipoprotein on admission and on the seventh day of hospitalization. We used a control group of 42 pediatric patients seen in emergency department without sepsis. Severity of disease was evaluated with Pediatric Risk of mortality score (PRISM) on admission and nutrition classification was performed in all patients. Results: CRP concentrations were very high on the first day of the study and had a significant reduction during evolution. On admission to the PICU, patients had significantly lower levels of TC, HDL, LDL as well as higher concentrations of TG in comparison with control group. There was a significant increase in the TC, HDL, LDL and apolipoprotein levels between the first and seventh days of the study. There was no relationship between the nutritional classification and lipoproteins levels. Conclusions: During the systemic inflammatory response we found lower serum levels of lipids and apolipoproteins with negative correlation in relation to CRP. As improvement in the inflammatory response, the levels of CT, HDL, LDL and apolipoprotein increased showing a direct relationship among changes in lipid profile and inflammation. Changes in lipid profile were not associated with nutritional status

La tuberculose (TB) reste la maladie infectieuse la plus meurtrière au monde. L’absence de développement de médicaments accompagnée de l'émergence de la résistance aux molécules existantes se traduit principalement par l'échec du traitement et la mort. M. tb infecte l'homme par l'inhalation. Le patient peut rester en bonne santé sans aucun symptôme, on parle alors de tuberculose latente. Dans ce cas, la bactérie résider dans le macrophage. La principale caractéristique de M. tb est de rester cacher à l'intérieur de ces cellules, puis se réactiver lorsque le système immunitaire s’affaibli.Mon travail a été consacrée à l'étude de nouveaux analogues de Cyclophostin / Cyclipostins (CyCs) et Oxadiazolone. Nombreuses molécules présentaient des activités antibactériennes lorsque la bactérie était cultivée dans le milieu liquide ou à l'intérieur du macrophage sans aucun effet toxique sur les macrophages.En utilisant le meilleur inhibiteur de CyC17, nous avons identifié 23 protéines cibles potentielles, étant impliquées dans le métabolisme des lipides de M. tb et / ou dans la biosynthèse des lipides de la paroi cellulaire. Parmi ces cibles, Ag85C et TesA, ont été caractérisées biochimiquement et structurallemnent.De plus, nous avons établi que les CyC sont des inhibiteurs puissants et sélectifs de la croissance des mycobactéries. De manière intéressante, ces composés étaient également actifs contre de nombreuses souches cliniques de M. abscessus, un pathogène opportuniste également appelés « cauchemars pour les antibiotiques », ouvrant ainsi la voie à la recherche de solutions alternatives pour lutter contre les souches mycobactériennes résistantes. / Tuberculosis (TB) is one of the deadliest infectious diseases worldwide. The stagnation in drug development accompanied with the emergence of drug resistance mainly results in treatment failure and death. M. tb infect human through inhalation. Patient can remains healthy without any symptom in which case it is known as latent TB. In latent TB, the bacteria is known to be reside in the macrophage - a type of white blood cell of the immune system, that engulfs and digests infected microorganisms. The famous characteristic of M. tb is the ability to stay inside and avoid to be killed by these cells, then reactivate when the immune system is weak.My work was devoted to the study of two series of new compounds, namely analogs of Cyclophostin/Cyclipostins (CyCs) and Oxadiazolone (OXs). Many molecules exhibited antibacterial activities when the bacteria was grown in the liquid medium or inside the macrophage without any toxic effect to the macrophages.Using the best CyC17 inhibitor, we identified 23 potential candidate target proteins, being involved in M. tb lipid metabolism and/or in cell wall lipid biosynthesis. Among these targets, two important protein, i.e. Ag85C and TesA, were biochemically and structurally characterized.Moreover, we clearly established that the CyCs are powerful and selective growth inhibitors of mycobacteria, with no effect on Gram-negative or Gram-positive bacteria. Interestingly, these compounds were also active against numerous M. abscessus clinical strains, an opportunistic pathogens also called “nightmare for antibiotic”, thus opening the way to find alternative solutions to fight against resistant mycobacterial strains.

A influência da obesidade sobre o fígado e a função hepática é tema ainda pouco estudado e discutido, principalmente no Brasil. O crescente aumento da população obesa de maneira global alerta sobre esse grave problema, que hoje em dia, se torna de saúde pública. Amplia-se, cada vez mais, o número de pessoas e a faixa etária atingida. A doença hepática não alcoólica é uma condição clínico-patológica comum caracterizada por depósitos de lipídios em hepatócitos no parênquima hepático. Um espectro de danos ocorrem no parênquima, desde uma simples esteatose macrogoticular podendo evoluir para esteato-hepatite, fibrose e até cirrose. Os casos de esteatose hepática não alcoólica (EHNA) que progridem para cirrose tem sido reconhecidos como a maior causa de morbidade e mortalidade com potencial para progredir para falência hepática. Apesar de haver um aumento na prevalência da doença hepática não alcoólica, os critérios para seu diagnóstico continuam pobremente definidos. A utilização da espectroscopia de prótons na ressonância magnética auxilia na quantificação do conteúdo lipídico hepático e na musculatura da perna (tibial anterior e sóleo), embora venha sendo utilizada apenas em pesquisas. Tivemos como objetivos o estudo do metabolismo lipídico de humanos xii obesos por espectroscopia por ressonância magnética, correlacionando com dados laboratoriais e de biópsias hepáticas. Neste estudo observacional transversal e prospectivo realizado em obesos, que foram submetidos a cirurgia redutora gástrica pela técnica de Capella no Hospital Prof. Edmundo Vasconcelos em São Paulo, foram incluídos 27 pacientes analisados no pré e pós-operatório para descrição dos dados. Foi constatada uma razão masculino/feminino geral de 8 :19 e a faixa etária entre 24 e 55 anos. Os índices de massa corpórea (IMC) eram sempre superiores a 40 Kg/m² para inclusão cirúrgica. Os pacientes obesos que no pré-operatório apresentavam esteatose hepática observada na ressonância magnética e esteatose e/ou esteato-hepatite na biópsia hepática evoluíram com melhora ou resolução no pós-operatório. Em conclusão, em pacientes obesos o grau de esteatose hepática pode ser analisado qualitativa e quantitativamente através da ressonância magnética com espectroscopia assim como, o controle pós tratamento cirúrgico evitando-se a utilização de métodos invasivos, entre eles a biópsia hepática. / The obesity influence on the liver and the hepatic function are themes that are not so discussed or studied, especially in Brazil. The world-wide increasing number of obese people calls the attention to this serious problem, that nowadays, became a public health problem. The number of people and the age of the people who suffer from it is increasing each day more. The non-alcoholic hepatic disease is a common pathological clinic condition caractherized by lipid deposits in hemocytes in the hepatic parenchyma. There are some injuries in the parenchyma, since a single steatosy macrogoticular to a steatohepatitis, a fibrosis and even a cirrhosis (Sass et al., 2005). The non-alcoholic steatosy hepatic (NASH) cases which lead to a cirrhosis have been known as the main causes of death with possibilities to evolute to a hepatic fail. Besides there is an increasing in the non-alcoholic hepatic disease, the means for its diagnosis still remain poorly defined. The protons spectroscopy use, in the magnetic resonance, helps on the lipidic hepatic contents numbers, although it has been used only for researches. We had as a goal the lipid metabolism study of obese human beings, related to the laboratorials data and the hepatic biopsy. On this study, where we observed obese people that were submitted to a gastric reducing surgery by the Capella techinic in the hospital Prof. Edmundo Vasconcelos in São Paulo, were included 27 pacients analyzed on the before and after operation for the datas description. It was noted a male/female general reason 9: 18 and the ages between 24 and 55 years old. The body mass indexes (IMC) were always over 40 Kg/m² to be included in a surgery. The obese patients who presented steatosy hepatic before operatory observed on the magnetic resonance and steatosy and/or steatohepatitis during the hepatic biosy went better on the pos-operatory. Finally, in obese patients the xiv steatosy hepatic degree can be analysed on its qualitativy and quantitativy through the magnetic resonance with spectroscopy, and so the cirurgical pos- treatment control, avoiding the use of invasive methods, among them the hepatic biopsy.

Background In some cross-sectional epidemiologic studies the shape of the association between serum concentrations of perfluoroalkyl acids (PFAAs) and lipids suggests departures from linearity. Objectives We used statistical approaches allowing for non-linearity to determine associations of prenatal exposures of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) with lipid concentrations. Methods PFAAs were measured in serum from pregnant women collected in 1991–1992 at enrollment in the Avon Longitudinal Study of Parents and Children and lipids in serum from their daughters at ages 7 (n = 111) and 15 (n = 88). The associations of PFAAs with lipids were first explored by cubic splines, followed by piecewise linear regressions by tertiles to obtain regression coefficients (β) and their 95% confidence limits (95% CL) (in mg/dL per 1 ng/mL). Results At age 7, total cholesterol was positively associated with prenatal PFOA concentrations in the lower tertile (β = 15.01; 95% CL = 2.34, 27.69) but not with PFOA concentrations in the middle (β = − 3.63; 95% CL = − 17.43, 10.16) and upper (β = − 1.58; 95% CL = − 4.58, 1.42) tertiles. At age 15, a similar pattern was noted as well. Positive associations between LDL-C and prenatal PFOA concentration in the lower tertile were observed in daughters at ages 7 (β = 14.91; 95% CL = 3.53, 28.12) and 15 (β = 13.93; 95% CL = 0.60, 27.26). LDL-C was not associated with PFOA concentrations in the middle or upper tertile at any age. Neither HDL-C nor triglycerides was associated with prenatal PFOA exposure. Non-linear patterns of association of total cholesterol and LDL-C with prenatal PFOS were less consistently noted. Conclusion Exposure to low levels of PFOA during prenatal development may alter lipid metabolism later in life. Given the small sample size further replication of the association in large independent cohorts is important.

Thesis (Ph.D.). / Written for the Dept. of Biology. Title from title page of PDF (viewed 2009/11/30). Includes bibliographical references.