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Doctoral Thesis
DOI
10.11606/T.5.2008.tde-04042008-155832
Document
Author
Full name
Vanessa Monteiro da Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Vinagre, Carmen Guilherme Christiano de Matos (President)
Martinez, Tania Leme da Rocha
Oliveira, Maria Rita Marques de
Rodrigues, Maria Rita
Xavier, Hermes Toros
Title in Portuguese
Metabolismo dos quilomícrons e capacidade da lipoproteína de alta densidade (HDL) de receber lípides na síndrome metabólica e no diabetes mellitus tipo 2
Keywords in Portuguese
Diabetes mellitus tipo 2
Emulsões
Lipoproteínas HDL
Quilomícrons
Síndrome X metabólica/metabolismo
Abstract in Portuguese
O principal distúrbio metabólico decorrente do Diabetes mellitus tipo 2 e da Síndrome Metabólica corresponde a alterações no metabolismo lipídico. Portanto, torna-se importante a melhor compreensão de alguns aspectos do metabolismo de lipoproteínas plasmáticas. Nesse sentido, a avaliação do metabolismo dos quilomícrons e da transferência de lípides de lipoproteínas plasmáticas para a lipoproteína de alta densidade (HDL), pode fornecer informações importantes relacionadas com o processo aterogênico. No presente estudo, foram estudados 15 indivíduos portadores de Diabetes mellitus tipo 2, 15 indivíduos com Síndrome Metabólica e 14 controles normolipidêmicos. Foi avaliada a cinética plasmática de uma nanoemulsão lipídica artificial com comportamento metabólico similar ao dos quilomícrons naturais, marcada com triglicérides (TG-3H) e éster de colesterol (EC-14C) radioativos. A nanoemulsão de quilomícrons artificiais foi injetada endovenosamente e amostras de sangue foram coletadas durante intervalos préestabelecidos. As curvas de decaimento plasmático dos lípides radioativos da nanoemulsão foram traçadas e as taxas fracionais de remoção (TFR) foram calculadas por análise compartimental. Para avaliação da transferência de lípides foi utilizada uma nanoemulsão semelhante a LDL (LDE) marcada com TG-3H e colesterol livre-14C (CL-14C) ou fosfolípides-14C (PL-14C) e EC-3H, como doadora de lípides para a HDL. Após incubação in vitro da LDE com o plasma, seguiu-se a precipitação das lipoproteínas que contem apolipoproteína B, restando no sobrenadante apenas a HDL. As taxas de transferência de lípides foram expressas em % de radioatividade encontrada no sobrenadante. Também foi determinado o diâmetro da HDL por espalhamento de luz. A TFR-EC dos grupos DM2 (p <0,05) e SM (p <0,01) comparado ao grupo controle apresentou-se diminuída, enquanto que as TFR-TG foram similares nos três grupos. Houve maior transferência de fosfolípides e colesterol nos grupos DM2 e SM comparando-se com grupo controle (p<0,001) A transferência de triglicérides e de éster de colesterol não diferiu entre os grupos. Não observou-se diferença no diâmetro da HDL nos três grupos. Concluindo, nossos resultados sugerem que a remoção plasmática dos remanescentes de quilomícrons encontra-se alterada em pacientes com SM e com DM2. Além disso, a transferência de lípides presentes na superfície das lipoproteínas para a HDL encontra-se aumentada nesses dois distúrbios metabólicos. Essas alterações podem contribuir com a maior incidência de aterosclerose nesses pacientes.
Title in English
Chylomicron metabolism and lipid reception capacity of high density lipoprotein in metabolic syndrome (MetS) and type 2 diabetes mellitus (DM2)
Keywords in English
Chylomicrons
Emulsions
HDL lipoproteins
Metabolic syndrome X/metabolism
Type 2 Diabetes mellitus
Abstract in English
The main metabolic disturbances occurring as a result of type 2 diabetes mellitus (DM2) and Metabolic Syndrome (MetS) are alterations in the metabolism of lipids. It is therefore, important to better understand the aspects by which plasma lipoproteins are metabolized. The evaluation of chylomicron metabolism and lipid transfer of high density lipoprotein (HDL) can thus yield useful information regarding the atherosclerotic process. In this study, 15 Type 2 Diabetes individuals, 15 Metabolic Syndrome individuals and 14 normolipidemic control individuals were studied. The plasmatic kinetics of an artificial lipidic nanoemulsion mimicking the behavior of natural chylomicrons were evaluated. This artificial chylomicron nanoemulsion, labele with radioactive triglycerides (TG-3H) and radioactive cholesteryl oleate (CO-14C) was injected intravenously and blood samples collected at pre-established time intervals. The plasmatic decay curve of the radioactive lipids of the nanoemulsion was traced and the fractional clearance rate calculated (FCR) through compartmental analysis. In order to evaluate the lipid transfer, we used a nanoemulsion similar to LDL., labeled with TG-3H and free cholesterol -14C (CL-14C) or with phospholipids -14C (PL-14C) and CO-3H, as a lipid donator to HDL. After in vitro nanoemulsion incubation with the plasma, the lipoproteins containing apolipoprotein B were precipitated, resulting in a supernatant containing HDL. The lipid transfer rates were expressed in % of radioactivity measured in the supernatant. It was also determined the diameter of the HDL using light scattering technique. The TFR-EC for the DM2 (p <0.05) and MetS (p <0.01) groups when compared to the control group was reduced. The TFR-TG, on the other hand, remained similar in all three groups. The transfer of phospholipids and cholesterol for the DM2 (p<0.001) and MetS groups was greater than that of the control group (p<0.001). The triglycerides and ester cholesteryl transfer showed no differences between the studied groups. Furthermore, no difference in HDL diameter was observed in any of the three groups. In conclusion, our results suggest that the removal of chylomicron remnants from the plasma is altered in SM and DM2 patients. Furthermore, there is an increase in the transfer of lipids located on the surface of lipoproteins to HDL . These alterations may contribute to a higher incidence of atherosclerosis in these patients.
 
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Publishing Date
2008-04-23
 
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