RESUMO
BACKGROUND: Triglyceride-rich lipoproteins (TRL: chylomicrons and VLDL) are a key component of diabetes dyslipoproteinemia and cardiovascular risk. We have shown that it is already prevalent in obese adolescents in association with lipoprotein lipase (LPL) dysregulation. Insulin resistance (IR) suffices to produce TRL dyslipoproteinemia and LPL dysfunction even in the absence of obesity. METHODS: This cross-sectional study included euglycemic adolescents between 15 and 19 y, classified in 4 groups according to BMI, HOMA-IR and fasting lipid as: metabolically healthy lean (MHL, n = 30), metabolically unhealthy lean (MUL, n = 25), metabolically healthy obese (MHO, = 30), and metabolically unhealthy obese (MUO, n = 42). RESULTS: As compared to MHL, MUL participants showed 73% higher concentrations of ApoB-48; 84% of ApoC-III; 24% ANGPTL-3; 200% of TG; 218% of VLDL-C and 238% of TG/HDL-C c, No changes were found in LPL mass. Interestingly, the differences in these parameters between MUL and MHO were not significant. CONCLUSION: Euglycemic lean adolescents with IR display TRL dyslipoproteinemia with increased inhibition of LPL as highlighted by higher concentrations of ANGPTL-3, ApoC-III and fasting chylomicron remnants (ApoB-48).
Assuntos
Proteína 3 Semelhante a Angiopoietina , Apolipoproteína C-III , Remanescentes de Quilomícrons , Dislipidemias , Resistência à Insulina , Adolescente , Estudos Transversais , Humanos , TriglicerídeosRESUMO
OBJECTIVE: Reductions on the clearance from plasma of chylomicrons are associated with atherosclerosis. Statins improve the removal from plasma of chylomicrons in a dose dependent manner. There is controversy whether ezetimibe modifies the plasma clearance of chylomicrons. Effects of ezetimibe alone or in combination with simvastatin were compared with low and high dose of the latter, upon the kinetics of a chylomicron-like emulsion in coronary heart disease (CHD) patients. METHODS: 25 CHD patients were randomized for treatment with ezetimibe 10 mg (group 1) or simvastatin 20 mg (group 2) with progression to ezetimibe + simvastatin 10/20 mg or simvastatin 80 mg, respectively. Kinetic studies were performed at baseline and after each treatment period of 6 weeks. The fractional catabolic rates (FCR) of the emulsion labeled with (14)C-CE and (3)H-TG, that represent respectively chylomicron remnant and triglyceride removal, were calculated. Comparisons were made by ANOVA. RESULTS: The (14)CE-FCR in group 1 were 0.005 ± 0.004, 0.011 ± 0.008 and 0.018 ± 0.005 min(-1) and in group 2 were 0.004 ± 0.003, 0.011 ± 0.008 and 0.019 ± 0.007 min(-1) respectively at baseline, after 6 and 12 weeks (p < 0.05 vs. baseline, and 6 vs. 12 weeks). The (3)H-TG-FCR in group 1 were 0.017 ± 0.011, 0.024 ± 0.011 and 0.042 ± 0.013 min(-1) and in group 2 were 0.016 ± 0.009, 0.022 ± 0.009 and 0.037 ± 0.012 min(-1) at baseline, after 6 and 12 weeks (p < 0.05 vs. baseline, and 6 vs. 12 weeks). There were no differences between groups in time. CONCLUSION: Both treatments increased similarly the removal from plasma of chylomicron and remnants in CHD patients.
Assuntos
Azetidinas/administração & dosagem , Quilomícrons/metabolismo , Doença das Coronárias/tratamento farmacológico , Sinvastatina/administração & dosagem , Idoso , Ésteres do Colesterol/metabolismo , Remanescentes de Quilomícrons/metabolismo , Quilomícrons/sangue , Doença das Coronárias/sangue , Quimioterapia Combinada , Ezetimiba , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Trioleína/metabolismoRESUMO
PURPOSE: Previously, it was showed that vegan diet improves the metabolism of triglyceride-rich lipoproteins by increasing the plasma clearance of atherogenic remnants. The aim of the current study was to investigate this metabolism in lacto-ovo vegetarians whose diet is less strict, allowing the ingestion of eggs and milk. Transfer of lipids to HDL, an important step in HDL metabolism, was tested in vitro. METHODS: Eighteen lacto-ovo vegetarians and 29 omnivorous subjects, all eutrophic and normolipidemic, were intravenously injected with triglyceride-rich emulsions labeled with ¹4C-cholesterol oleate and ³H-triolein. Fractional clearance rates (FCR, in min⻹) were calculated from samples collected during 60 min. Lipid transfer to HDL was assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids. RESULTS: LDL cholesterol was lower in vegetarians than in omnivores (2.1 ± 0.8 and 2.7 ± 0.7 mmol/L, respectively, p < 0.05), but HDL cholesterol and triglycerides were equal. Cholesteryl ester FCR was greater in vegetarians than in omnivores (0.016 ± 0.012, 0.003 ± 0.003, p < 0.01), whereas triglyceride FCR was equal. Cholesteryl ester transfer to HDL was lower in vegetarians than in omnivores (2.7 ± 0.6, 3.5 ± 1.5 %, p < 0.05), but free cholesterol, triglyceride and phospholipid transfers and HDL size were equal. CONCLUSION: Similarly to vegans, lacto-ovo vegetarian diet increases remnant removal, as indicated by cholesteryl oleate FCR, which may favor atherosclerosis prevention, and has the ability to change lipid transfer to HDL.
Assuntos
Aterosclerose/prevenção & controle , Remanescentes de Quilomícrons/metabolismo , Dieta Vegetariana , Gorduras na Dieta/metabolismo , Ovos/efeitos adversos , Lipoproteínas HDL/metabolismo , Leite/efeitos adversos , Adulto , Animais , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/metabolismo , Transporte Biológico , Brasil/epidemiologia , Radioisótopos de Carbono , Remanescentes de Quilomícrons/sangue , Emulsões , Feminino , Humanos , Cinética , Lipoproteínas HDL/sangue , Masculino , Carne/efeitos adversos , Fatores de Risco , TrítioRESUMO
Chylomicron remnants bind to both their specific receptors (LRP) and to the LDL receptor (LDLR) in the liver. There is controversy whether disturbances of chylomicron metabolism occur in subjects with familial hypercholesterolemia (FH). The aim of this study was to evaluate whether there are defects on the removal from plasma of chylomicrons and their remnants in heterozygous FH patients with determined LDLR mutations. We studied 20 heterozygous FH patients (43.2±12 years old, 60% males) and 50 normolipidemic subjects matched for age and gender. FH subjects were not in use of LDL-lowering drugs for at least 6 weeks. The removal from plasma of chylomicrons and their remnants was measured by isotopic decay after venous injection of a chylomicron-like emulsion radiolabeled with (14)C-cholesteryl ester ((14)C-CE) and (3)H-triolein ((3)H-TO). These track respectively removal from plasma of chylomicrons and remnants and lipolysis. There was a significant reduction in the fractional catabolic rates (FCR in h(-1)) of (14)C-CE in FH in comparison with normolipidemics: 0.048 (1.46.10(-7); 0.57) vs. 0.71(0.049; 1.62), [median (25th-75th percentile)], p=0.003. No differences were found in FCR of (3)H-TO between FH and controls, respectively 1.62 (1.02; 2.331) and 1.914 (1.34; 2.878), p=0.405. In conclusion heterozygous FH subjects had a significant decrease on the removal from plasma of chylomicrons and their remnants compared with normolipidemics.
Assuntos
Remanescentes de Quilomícrons/sangue , Quilomícrons/sangue , Heterozigoto , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/genética , Mutação , Receptores de LDL/genética , Adulto , Brasil , Radioisótopos de Carbono , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Ésteres do Colesterol/administração & dosagem , Ésteres do Colesterol/sangue , Ésteres do Colesterol/farmacocinética , Emulsões , Feminino , Predisposição Genética para Doença , Humanos , Injeções Intravenosas , Lipólise , Masculino , Pessoa de Meia-Idade , Fenótipo , Trioleína/administração & dosagem , Trioleína/farmacocinética , TrítioRESUMO
Remnant lipoproteins (RLPs) are the lipolytic product of triglycerides transported by very low density lipoproteins (VLDL) of hepatic and intestinal origin and intestinal chylomicrons. Lipoprotein lipase activity hydrolyse triglycerides in several steps, producing heterogeneous particles. Fasting plasma concentration in normolipidemic subjects is low, but it increases in post-prandial states. Genetic alterations in Apo-E subtypes increases RLPs plasma concentration and produce dyslipoproteinemia phenotype. RLPs atherogenicity depends on their role as endothelial injuring factors, their impaired recognition by lipoprotein receptors, and their susceptibility to oxidative stress. They also promote the circulation of molecular adhesion molecules, the internalization in subendothelial macrophages via scavenger receptors and the accumulation in foam cells, all of them early mechanisms of atheromatosis. RLPs metabolism has been a subject of controversial studies. Their origin from different lipoproteins may explain their structural heterogeneity, therefore increasing the methodological difficulties to include RLPs in the atherogenic lipoprotein profile in the epidemiological studies of the field. Last advances on metabolism of RLPs and their emergent clinical role justifies an up dated revision of RLPs.
Assuntos
Aterosclerose/sangue , Lipoproteínas/sangue , Remanescentes de Quilomícrons/sangue , Humanos , Lipoproteínas LDL/sangueRESUMO
La lipoproteínas remanentes (RLPs) son el producto de la lipólisis de los triglicéridos transportados por las lipoproteínas de baja densidad (VLDL) de origen hepático e intestinal y de los quilomicrones intestinales. Dicha lipólisis es catalizada por la lipoproteína lipasa y se produce en pasos sucesivos, de manera que los productos son heterogéneos. Su concentración plasmática en ayunas es pequeña en pacientes normolipémicos y aumenta en el estado post-prandial. Las alteraciones genéticas en subtipos de su componente Apo-E aumentan notablemente su concentración plasmática y producen el fenotipo de disbetalipoproteinemia. Se las considera aterogénicas porque injurian el endotelio, sufren estrés oxidativo, son captadas por los macrófagos en el subendotelio vascular y generan las células espumosas que son precursoras de ateromas. Su origen metabólico, como productos de varios tipos de lipoproteínas, explican su estructura heterogénea, sus concentraciones plasmáticas variables y las dificultades metodológicas que dificultan su inclusión en el perfil lipoproteico como parte de los estudios epidemiológicos. Los últimos avances en los estudios metabólicos y la actualización de su papel clínico, justifican una revisión de los conocimientos actuales.
Remnant lipoproteins (RLPs) are the lipolytic product of triglycerides transported by very low density lipoproteins (VLDL) of hepatic and intestinal origin and intestinal chylomicrons. Lipoprotein lipase activity hydrolyse triglycerides in several steps, producing heterogeneous particles. Fasting plasma concentration in normolipidemic subjects is low, but it increases in post-prandial states. Genetic alterations in Apo-E subtypes increases RLPs plasma concentration and produce dyslipoproteinemia phenotype. RLPs atherogenicity depends on their role as endothelial injuring factors, their impaired recognition by lipoprotein receptors, and their susceptibility to oxidative stress. They also promote the circulation of molecular adhesion molecules, the internalization in subendothelial macrophages via scavenger receptors and the accumulation in foam cells, all of them early mechanisms of atheromatosis. RLPs metabolism has been a subject of controversial studies. Their origin from different lipoproteins may explain their structural heterogeneity, therefore increasing the methodological difficulties to include RLPs in the atherogenic lipoprotein profile in the epidemiological studies of the field. Last advances on metabolism of RLPs and their emergent clinical role justifies an up dated revision of RLPs.