scholarly journals Apolipoprotein C1: Its Pleiotropic Effects in Lipid Metabolism and Beyond

2019 ◽  
Vol 20 (23) ◽  
pp. 5939 ◽  
Author(s):  
Elena V. Fuior ◽  
Anca V. Gafencu
Keyword(s):  
Therapeutic Potential ◽  
Hepatic Lipase ◽  
Duplicate Gene ◽  
Lipoprotein Receptors ◽  
Cholesterol Acyl Transferase ◽  
Lecithin Cholesterol Acyl Transferase ◽  
Transfer Protein ◽  
Non Coding Rna ◽  
Biophysical Studies ◽  
Regulatory Properties

Apolipoprotein C1 (apoC1), the smallest of all apolipoproteins, participates in lipid transport and metabolism. In humans, APOC1 gene is in linkage disequilibrium with APOE gene on chromosome 19, a proximity that spurred its investigation. Apolipoprotein C1 associates with triglyceride-rich lipoproteins and HDL and exchanges between lipoprotein classes. These interactions occur via amphipathic helix motifs, as demonstrated by biophysical studies on the wild-type polypeptide and representative mutants. Apolipoprotein C1 acts on lipoprotein receptors by inhibiting binding mediated by apolipoprotein E, and modulating the activities of several enzymes. Thus, apoC1 downregulates lipoprotein lipase, hepatic lipase, phospholipase A2, cholesterylester transfer protein, and activates lecithin-cholesterol acyl transferase. By controlling the plasma levels of lipids, apoC1 relates directly to cardiovascular physiology, but its activity extends beyond, to inflammation and immunity, sepsis, diabetes, cancer, viral infectivity, and—not last—to cognition. Such correlations were established based on studies using transgenic mice, associated in the recent years with GWAS, transcriptomic and proteomic analyses. The presence of a duplicate gene, pseudogene APOC1P, stimulated evolutionary studies and more recently, the regulatory properties of the corresponding non-coding RNA are steadily emerging. Nonetheless, this prototypical apolipoprotein is still underexplored and deserves further research for understanding its physiology and exploiting its therapeutic potential.

scholarly journals ApoE and apoC-III-defined HDL subtypes: A descriptive study of their lecithin cholesterol acyl transferase and cholesteryl ester transfer protein content and activity

2020 ◽  
Author(s):  
Mateo Amaya-Montoya ◽  
Jairo A Pinzón-Cortés ◽  
Lina S Silva-Bermúdez ◽  
Daniel Ruiz-Manco ◽  
Maria C Perez-Matos ◽  
...  
Keyword(s):  
Size Distribution ◽  
Plasma Cholesterol ◽  
Inverse Correlation ◽  
High Density Lipoproteins ◽  
Acyl Transferase ◽  
Lcat Activity ◽  
Cholesterol Acyl Transferase ◽  
Lecithin Cholesterol Acyl Transferase ◽  
Transfer Protein ◽  
Plasma Lcat

Abstract Background The functionality of high-density lipoproteins (HDL) is a better cardiovascular risk predictor than HDL concentrations. One of the key elements of HDL functionality is its apolipoprotein composition. Lecithin-cholesterol acyl transferase (LCAT) and cholesterol-ester transfer protein (CETP) are enzymes involved in HDL-mediated reverse cholesterol transport. This study assessed the concentration and activity of LCAT and CETP in HDL subspecies defined by their content of apolipoproteins E (apoE) and C-III (apoC-III) in humans. Methods Eighteen adults (ten women and eight men, mean age 55.6, BMI 26.9 Kg/m 2 , HbA1c 5.4%) were studied. HDL from each participant were isolated and divided into four subspecies containing respectively: No apoE and no apoC-III (E-C-), apoE but not apoC-III (E+C-), apoC-III but no apoE (E-C+) and both apoE and apoC-III (E+C+). The concentration and enzymatic activity of LCAT and CETP were measured within each HDL subspecies using immunoenzymatic and fluorometric methods. Additionally, the size distribution of HDL in each apolipoprotein-defined fraction was determined using non-denaturing electrophoresis and anti-apoA-I western blotting. Results HDL without apoE or apoC-III was the predominant HDL subtype. The size distribution of HDL was very similar in all the four apolipoprotein-defined subtypes. LCAT was most abundant in E-C- HDL (3.58 mg/mL, 59.6 % of plasma LCAT mass), while HDL with apoE or apoC-III had much less LCAT (19.8%, 12.2% and 8.37% of plasma LCAT respectively for E+C-, E-C+ and E+C+). LCAT mass was lower in E+C- HDL relative to E-C- HDL, but LCAT activity was similar in both fractions, signaling a greater activity-to-mass ratio associated with the presence of apoE. Both CETP mass and CETP activity showed only slight variations across HDL subspecies. There was an inverse correlation between plasma LCAT activity and concentrations of both E-C+ pre-beta HDL (r=-0.55, P =0.017) and E-C- alpha 1 HDL (r=-0.49, P =0.041). Conversely, there was a direct correlation between plasma CETP activity and concentrations of E-C+ alpha 1 HDL (r=0.52, P =0.025). Conclusions The presence of apoE in small HDL is correlated with increased LCAT activity and esterification of plasma cholesterol. These results favor an interpretation that LCAT and apoE interact to enhance anti-atherogenic pathways of HDL.

scholarly journals ApoE and apoC-III-defined HDL subtypes: A descriptive study of their LCAT and CETP content and activity

2020 ◽  
Author(s):  
Mateo Amaya-Montoya ◽  
Jairo A Pinzón-Cortés ◽  
Lina S Silva-Bermúdez ◽  
Daniel Ruiz-Manco ◽  
Maria C Perez-Matos ◽  
...  
Keyword(s):  
Size Distribution ◽  
Plasma Cholesterol ◽  
Inverse Correlation ◽  
High Density Lipoproteins ◽  
Lcat Activity ◽  
Cholesterol Acyl Transferase ◽  
Lecithin Cholesterol Acyl Transferase ◽  
Transfer Protein ◽  
Plasma Lcat ◽  
Apolipoproteins E

Abstract Background High-density lipoproteins (HDL) in plasma are strongly and negatively associated with cardiovascular risk, yet interventions to raise HDL have not improved cardiovascular outcomes. HDL functionality and heterogeneity may hold the clue to this paradox. The apolipoprotein composition of HDL may be an important determinant of their functionality. Lecithin-cholesterol acyl transferase (LCAT) and cholesterol-ester transfer protein (CETP) are key enzymes for HDL-mediated reverse cholesterol transport. We assessed the distribution and activity of LCAT and CETP in HDL subspecies defined by their content of apolipoproteins E (apoE) and C-III (apoC-III) in humans. Methods We isolated in adult humans of both sexes (mean age 55.6, BMI 26.9 Kg/m2, HbA1c 5.4%), four subspecies of HDL containing respectively: No apoE and no apoC-III (E-C-), apoE but not apoC-III (E+C-), apoC-III but no apoE (E-C+) and both apoE and apoC-III (E+C+). In each HDL subspecies, we measured LCAT and CETP concentration and activity using immunoenzymatic and fluorometric methods. Additionally, we determined the size distribution of HDL in each apolipoprotein-defined fraction using non-denaturing electrophoresis and anti-ApoA-I western blot. Results Similar to previous studies, HDL in the E-C- fraction was the predominant subtype. The size distribution of HDL was very similar across all four apolipoprotein-defined fractions. LCAT was most abundant in E-C- HDL (3.58 mg/mL, 59.6 % of plasma LCAT mass), while HDL with apoE or apoC-III had much less LCAT (19.8%, 12.2% and 8.37% of plasma LCAT respectively for E+C-, E-C+ and E+C+). Despite a much lower LCAT mass, LCAT activity in E+C- HDL was comparable to that in E-C- HDL. Both CETP mass and CETP activity showed only slight variations across HDL subspecies. There was an inverse correlation between plasma LCAT activity and both E-C+ pre-beta HDL (r=-0.55, p=0.017) and E-C- alpha 1 HDL (r=-0.49, p=0.041). Conversely, there was a direct correlation between E-C+ alpha 1 HDL and CETP activity in plasma (r=0.52, p=0.025). Conclusions Our results suggest that LCAT activity in humans is influenced by the presence of small interchangeable apolipoproteins. The presence of apoE in small HDL is correlated with increased LCAT activity and esterification of plasma cholesterol.

scholarly journals Relations Between Atherogenic Index of Plasma, Ratio of Small Dense Low Density Lipoprotein/Lecithin Cholesterol Acyl Transferase and Ratio of Small Dense Low Density Lipoprotein/Cholesteryl Ester Transfer Protein of Controlled and Uncontrolled Type 2 DM

2009 ◽  
Vol 1 (2) ◽  
pp. 38
Author(s):  
Ellis Susanti ◽  
Marsetio Donosepoetro ◽  
Gatot Susilo Lawrence
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Atherogenic Index ◽  
Low Density ◽  
Cholesterol Acyl Transferase ◽  
Atherogenic Index Of Plasma ◽  
Lecithin Cholesterol Acyl Transferase ◽  
Small Dense Ldl ◽  
Transfer Protein

BACKGROUND: Patients with Diabetes Melitus are proven to be prone to atherosclerosis and coronary heart disease, especially type 2 Diabetes Melitus (T2DM) patient who have higher risk and mortality for cardiovascular risk factor. The Dyslipidemia condition is very common in T2DM as one of the risk factors. Diabetic dyslipidemia is marked by the increased triglyceride (TG), low HDL cholesterol (HDL-C), and increased small dense LDL and apolipoprotein B. Therefore the aim of this study is to assess the differential and correlation between Atherogenic Index of Plasma (AIP), ratio of small dense low density lipoprotein (sdLDL)/lecithin cholesterol acyl transferase (LCAT) and ratio of sdLDL/cholesteryl ester transfer protein (CETP) of controlled and uncontrolled T2DM.METHODS: This study was observational with cross sectional design. In total of 72 patients with T2DM consist of 36 controlled and 36 uncontrolled, participated in this study. The serum TG, HDL-C, sdLDL, LCAT and CETP were examined in their relationship with to T2DM risk.RESULTS: The results of the study indicate that the AIP (p<0.001) increase controlled and uncontrolled T2DM and the ratio of sdLDL/CETP (p=0.004), odds ratio of AIP was 4 (95% CI : 1.501-10.658) and odds ratio of sdLDL/CETP ratio was 4 (95% CI : 1.501-10.658) in uncontrolled T2DM.CONCLUSION: This study showed that the AIP and ratio of small dense LDL/CETP had a significant correlation with the uncontrolled T2DM. The AIP and ratio of small dense LDL/CETP increase was found at the uncontrolled T2DM to be 4 times greater than the controlled T2DM.KEYWORDS: T2DM, atherosclerosis, atherogenic index of plasma, small dense LDL, LCAT, CETP, ratio of sdLDL/LCAT, ratio of sdLDL/CETP

scholarly journals Diabetes, Obesidad y Lípidos

2017 ◽  
Vol 4 (2) ◽  
pp. 60-76
Author(s):  
Asociación Colombiana de Endocrinología Diabetes & Metabolismo
Keyword(s):  
Diabetes Mellitus ◽  
Moderate Intensity ◽  
Cholesterol Acyl Transferase ◽  
Lecithin Cholesterol Acyl Transferase ◽  
Transfer Protein ◽  
Apolipoprotein C ◽  
Síndrome Metabólico ◽  
Factores De Riesgo ◽  
Control Glucémico ◽  
Intensity Training

Listado Apolipoprotein E and apolipoprotein C-III-defined HDL Subspecies differ in their lecithin-cholesterol acyl transferase and cholesterol-ester transfer protein content and activity.  Amaya-Montoya M, Pinzón-Cortés JA, Silva-Bermúdez LS, Ruiz-Manco D, Pérez-Matos MC, Mendivil CO Efecto del uso de metformina sobre el perfil tiroideo en pacientes con síndrome de ovarios poliquísticos.  Cano RA, Agostini MI, Corzo GA, Cano C, Figueroa L. Características epidemiológicas y clínicas de una cohorte de adultos con cetoacidosis diabética atendidos en un hospital universitario de Colombia. Estudio CAD-EPI.  MANIPURA Diagnóstico prenatal de inversión pericéntrica del cromosoma 9 y su asociación con enfermedades metabólicas.  Usta C, Torres C, Gómez M, Lynett D, Fernández I, Celis LG. Estrategias para el control del sobrepeso y prevención de la obesidad en la población escolar: una revisión narrativa.  Amador E., Montealegre L. Asociación entre variantes en el gen del receptor 1 de adiponectina (ADIPOR1) con diabetes e hipertrigliceridemia en adultos del caribe colombiano. Ruiz Díaz MS, Mora García GJ, Espitia F, Flórez D, Gómez Camargo DE Control glucémico en pacientes hospitalizados en sala general con hiperglucemia en tratamiento con insulinoterapia: situación actual de una clínica de cuarto nivel de atención en el oriente colombiano.  Hernández BM, Sánchez ML, Parra GA Estudio de enfermedades crónico-degenerativas, factores de riesgo cardiovascular en escolares. Abordaje desde la medicina traslacional.  Celis LG, Russi A, Mendieta Zerón H, Ayala J, Giratá V y Almonacid C. Factores de riesgo para hipertensión arterial en el área rural de Quingeo, Ecuador, 2016.  Rina Ortiz, Maritza Torres, Susana Peña, Roberto Añez, Valmore Bermúdez Hemoglobina glucosilada no contribuye al diagnóstico de DM2 y prediabetes en la población colombiana.  DIOGENES DE SINOPE II Consenso Latinoamericano de Obesidad.  Gómez-Cuevas R., Valenzuela A., Nuila M., Ponce M.L., Deras J., DeLeon C, Aure G., Aguirre H., González J., Marin S., Rojas M.I., Ribera R., Halpern B, Jiménez M.C. Recalde A, Lobato G. Impacto de los edulcorantes sobre los receptores de insulina y la microbiota intestinal, como factores relacionados con la aparición de la diabetes mellitus.  Cadena Silvia Indicadores antropométricos como factores de riesgo de hipertensión arterial en estudiantes de la Universidad Metropolitana de Barranquilla.  Carmen María Carrero Respuesta aguda del perfil lipídico a dos modalidades de ejercicio físico en mujeres posmenopáusicas.  Edmund Halley Liraglutide en el tratamiento de hipoglucemia posprandial como complicación de un bypass gástrico. Reporte de un caso.  Guzmán G, Gutiérrez K, Plaza L, Martínez V. Similar cardiometabolic effects of high- versus moderate-intensity training among apparently healthy inactive adults. A randomized clinical trial.  Ramírez-Vélez R; Correa-Bautista JE. Manejo de hiperglucemia inducida por esteroides con esquema de insulina NPH en pacientes diabéticos hospitalizados en una unidad de hemato-oncología: resultados de una cohorte prospectiva.  Parra GA, Velandia CA, Rodríguez, JD, Ojeda JD, Pérez YT, Osma OO. Prevalencia y factores asociados a la obesidad en el área rural de Cumbe, Ecuador, 2016.  Torres M., Ortiz R., Añez R., Delgado F., Bermúdez V., Peña Susana Proyecto PREDICOL: programa de atención en salud comunitaria para la prevención de diabetes tipo 2 y otros factores de riesgo en personas adultas desde atención primaria en los distritos de Barranquilla y Bogotá, 2017-2019.  Acosta T., Aschner P., Acosta J., Carvajal L., Navarro E. Proteoma de tejido adiposo subcutáneo en individuos con obesidad, antes y después de cirugía bariátrica. Moreno N.R, Vázquez-Martínez R. y Malagón M.M. Puede ayudar la actividad física al control de la diabetes mellitus: revisión de la evidencia.  Lara G. Reducción de la variabilidad glucémica (VG) a las 12 de semanas de tratamiento con insulina Degludec (IDeg) en individuos con diabetes mellitus tipo 1 (DM1) y tipo 2 (DM2) con hipoglucemia medida por monitoreo continuo de glucosa (MCG) retrospectivo.  Henao D, Gómez AM, Muñoz O, Rondón M, Colon C, Chica L, Rubio C, León F. Respuesta cardiopulmonar y glucémica en pacientes diabéticos en posquirúrgico cardiovascular luego de un programa de entrenamiento aeróbico interválico.  JP Aspectos demográficos de una muestra de pacientes colombianos con diabetes mellitus tipo 1. Diana Clobeth Sarrazola Yepes, Natalia Gómez-Lopera, Jorge García, María Victoria Lopera, Martín Toro, Alejandra Vélez, Juan Manuel Alfaro y Nicolás Pineda-Trujillo Síndrome metabólico en pacientes en posquirúrgico cardiovascular.  Pereira JE; Pereira R; Boada L; Peñaranda D. Diferencias en las relaciones entre las masas mineral, magra y grasa del cuerpo entero en 600 hombres y mujeres pre y posmenopáusicas colombianas de hábitos urbanos o rurales.  Cure Cure C MD, Ferretti J L, Cure P, López Jaramillo JP, Nocciolino L, Luscher S, Capozza R. Una variante en el gen RNASEH1 interactúa con tagSNPs de HLA en familias colombianas con diabetes mellitus tipo 1.  Gómez-Lopera N., Sarrazola Yepes D., Toro M., Lopera M., Alfaro J-M., Pineda-Trujillo N. Variabilidad glucémica asociada a lipohipertrofia en paciente con uso de bomba de infusión de insulina con suspensión automática en hipoglucemia. Reporte de caso.  Parra GA, Aristizábal SM

scholarly journals ApoE and apoC-III-defined HDL subtypes: A descriptive study of their LCAT and CETP content and activity

2020 ◽  
Author(s):  
Mateo Amaya-Montoya ◽  
Jairo A Pinzón-Cortés ◽  
Lina S Silva-Bermúdez ◽  
Daniel Ruiz-Manco ◽  
Maria C Perez-Matos ◽  
...  
Keyword(s):  
Size Distribution ◽  
Plasma Cholesterol ◽  
Inverse Correlation ◽  
High Density Lipoproteins ◽  
Lcat Activity ◽  
Cholesterol Acyl Transferase ◽  
Lecithin Cholesterol Acyl Transferase ◽  
Transfer Protein ◽  
Plasma Lcat ◽  
Apolipoproteins E

Abstract Background High-density lipoproteins (HDL) functionality predicts cardiovascular risk better than HDL concentrations. The apolipoprotein composition of HDL may be a determinant of their function. Lecithin-cholesterol acyl transferase (LCAT) and cholesterol-ester transfer protein (CETP) are key enzymes for HDL-mediated reverse cholesterol transport. We assessed the distribution and activity of LCAT and CETP in HDL subspecies defined by their content of apolipoproteins E (apoE) and C-III (apoC-III) in humans. Methods We isolated in 18 adult humans of both sexes (mean age 55.6, BMI 26.9 Kg/m2, HbA1c 5.4%), four subspecies of HDL containing respectively: No apoE and no apoC-III (E-C-), apoE but not apoC-III (E+C-), apoC-III but no apoE (E-C+) and both apoE and apoC-III (E+C+). In each HDL subspecies, we measured LCAT and CETP concentration and activity using immunoenzymatic and fluorometric methods. Additionally, we determined the size distribution of HDL in each apolipoprotein-defined fraction using non-denaturing electrophoresis and anti-ApoA-I western blot. Results Similar to previous studies, HDL in the E-C- fraction was the predominant subtype. The size distribution of HDL was very similar across all four apolipoprotein-defined fractions. LCAT was most abundant in E-C- HDL (3.58 mg/mL, 59.6 % of plasma LCAT mass), while HDL with apoE or apoC-III had much less LCAT (19.8%, 12.2% and 8.37% of plasma LCAT respectively for E+C-, E-C+ and E+C+). LCAT mass was lower in E+C- HDL relative to E-C- HDL, but LCAT activity was similar in both fractions, signaling a greater activity-to-mass ratio associated with the presence of apoE. Both CETP mass and CETP activity showed only slight variations across HDL subspecies. There was an inverse correlation between plasma LCAT activity and both E-C+ pre-beta HDL (r=-0.55, p=0.017) and E-C- alpha 1 HDL (r=-0.49, p=0.041). Conversely, there was a direct correlation between E-C+ alpha 1 HDL and CETP activity in plasma (r=0.52, p=0.025). Conclusions Our results suggest that LCAT activity in humans is influenced by the presence of small interchangeable apolipoproteins. The presence of apoE in small HDL is correlated with increased LCAT activity and esterification of plasma cholesterol.

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