RESUMEN
AIMS: Little is known about the regulation of phospholipid transfer protein (PLTP), that plays a key role in lipoprotein metabolism. PLTP secretion may be up-regulated by glucose in vitro, whereas plasma PLTP activity is decreased by exogenous hyperinsulinaemia and glucose-induced hyperinsulinaemia in vivo. In the present study, we evaluated the separate effects of hyperglycaemia and hyperinsulinaemia in C-peptide-negative Type 1 diabetic patients. METHODS: The protocol was carried out in 16 patients (eight females). In each individual, plasma PLTP mass and activity (measured by enzyme-linked immuno-sorbent assay and liposome-high density lipoprotein system, respectively) as well as plasma cholesteryl ester transfer protein (CETP) activity, lipids and apolipoprotein levels were determined at the end of four different glucose clamps, each lasting 210 min: standard insulin (30 mU/kg/h) and standard glucose (glucose 5.0 mmol/l) (SI-SG), standard insulin and high glucose (glucose 12 mmol/l) (SI-HG), high insulin (150 mU/kg/h) and standard glucose (HI-SG), and high insulin and high glucose (HI-HG). RESULTS: Plasma lipids and (apo)lipoproteins, measured at the end of the SI-HG, HI-SG and HI-HG clamps, were not significantly different compared with the levels obtained at the end of the SI-SG clamp. Median plasma PLTP mass and activity at the end of the SI-SG clamp were 12.8 mg/l and 13.2 micromol/ml/h, respectively. Median plasma PLTP mass decreased by 9.1% at the end of the HI-HG clamp (P < 0.01), whereas the changes at the end of the SI-HG and HI-SG clamps were not significant. Median plasma PLTP activity decreased by 5.7, 4.6 and 8.6% at the end of the SI-HG, HI-SG and HI-HG clamps, respectively (all P < 0.05). Median plasma CETP activity was 177 nmol/ml/h at the end of the SI-SG clamp, and decreased by 4.9% (P < 0.05) and by 8.3% (P < 0.05) at the end of the HI-SG and the HI-HG clamps, respectively. Plasma CETP activity did not change significantly at the end of the SI-HG clamp. CONCLUSIONS: The present study demonstrates that plasma PLTP activity is independently decreased by acute hyperglycaemia and hyperinsulinaemia in humans in vivo. These data do not support a direct role of short-term hyperglycaemia in up-regulating plasma PLTP levels.
Asunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Hiperglucemia/sangre , Hiperinsulinismo/sangre , Proteínas de Transferencia de Fosfolípidos/metabolismo , Adulto , Glucemia/metabolismo , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Insulina/sangre , MasculinoRESUMEN
BACKGROUND: Human plasma contains two lipid transfer proteins, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), which are crucial in reverse cholesterol transport. METHODS: Plasma CETP and PLTP activity levels and concentrations in 16 type 2 diabetic patients and 16 matched healthy subjects were determined, and these data were correlated to clinical variables, including insulin sensitivity and lipid levels. RESULTS: Plasma triglycerides were higher (p<0.02) and high-density lipoprotein (HDL) cholesterol (p<0.02) was lower in diabetic patients. Plasma CETP activity and concentrations were not significantly different between diabetic and healthy subjects, but CETP specific activity was lower in diabetic patients (p<0.001). Multiple regression analysis showed that plasma CETP activity was positively related to CETP concentration (p=0.0001) and negatively to the diabetic state (p<0.002) or to HbA1c (p<0.02). PLTP activity (p<0.05) and specific activity were higher (p<0.05), whereas there was no difference in PLTP concentration between the two groups. There was no significant bivariate correlation between PLTP concentration and activity, in either healthy or diabetic subjects. Multiple regression analysis did disclose positive relationships of PLTP activity with PLTP concentration (p=0.0001), plasma triglycerides (p=0.0001) and waist/hip ratio (p=0.0001), but not with the diabetic state or HbA1c. CONCLUSIONS: Neither CETP nor PLTP activity was independently associated with insulin sensitivity. Specific CETP activity is decreased in type 2 diabetes mellitus. In contrast, specific PLTP activity is higher in diabetes, as a result of the association of plasma PLTP activity with plasma triglycerides and obesity. Measurement of both plasma lipid transfer protein activity and mass levels may thus provide extra information in diabetes mellitus.
Asunto(s)
Proteínas Portadoras/sangre , Diabetes Mellitus Tipo 2/sangre , Glicoproteínas/sangre , Proteínas de la Membrana/sangre , Proteínas de Transferencia de Fosfolípidos/sangre , Apolipoproteínas/sangre , Glucemia/análisis , Composición Corporal , Índice de Masa Corporal , Colesterol/sangre , Proteínas de Transferencia de Ésteres de Colesterol , Técnica de Clampeo de la Glucosa , Hemoglobina Glucada/análisis , Humanos , Insulina/sangre , Lipoproteínas/sangre , Persona de Mediana Edad , Análisis de Regresión , Estadísticas no Paramétricas , Triglicéridos/sangre , Relación Cintura-CaderaRESUMEN
Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol pathway: cellular cholesterol efflux and plasma cholesterol esterification. Eleven healthy middle-aged men consumed four glasses (40 g of alcohol) of red wine, beer, spirits (Dutch gin), or carbonated mineral water (control) daily with evening dinner, for 3 weeks, according to a 4 x 4 Latin square design. After 3 weeks of alcohol consumption the plasma ex vivo cholesterol efflux capacity, measured with Fu5AH cells, was raised by 6.2% (P < 0.0001) and did not differ between the alcoholic beverages. Plasma cholesterol esterification was increased by 10.8% after alcohol (P = 0.008). Changes were statistically significant after beer and spirits, but not after red wine consumption (P = 0.16). HDL lipids changed after alcohol consumption; HDL total cholesterol, HDL cholesteryl ester, HDL free cholesterol, HDL phospholipids and plasma apolipoprotein A-I all increased (P < 0.01). In conclusion, alcohol consumption stimulates cellular cholesterol efflux and its esterification in plasma. These effects were mostly independent of the kind of alcoholic beverage
Asunto(s)
Consumo de Bebidas Alcohólicas/metabolismo , Colesterol/metabolismo , Etanol/farmacología , Consumo de Bebidas Alcohólicas/sangre , Apolipoproteína A-I/metabolismo , Cerveza , Transporte Biológico/efectos de los fármacos , Colesterol/sangre , Ésteres del Colesterol/metabolismo , Esterificación/efectos de los fármacos , Etanol/sangre , Etanol/uso terapéutico , Humanos , Lipoproteínas HDL/metabolismo , Masculino , Persona de Mediana Edad , Fosfolípidos/metabolismo , Periodo Posprandial/efectos de los fármacos , Factores de Tiempo , Triglicéridos/metabolismo , VinoRESUMEN
High-density lipoproteins (HDLs) are considered anti-atherogenic because they mediate peripheral cell cholesterol transport to the liver for excretion and degradation. An important step in this reverse cholesterol-transport pathway is the uptake of cellular cholesterol by a specific subclass of small, lipid-poor apolipoprotein A-I particles designated pre beta-HDL. The two lipid-transfer proteins present in human plasma, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), have both been implicated in the formation of pre beta-HDL. In order to investigate the relative contribution of each of these proteins, we used transgenic mouse models. Comparisons were made between human CETP transgenic mice (huCETPtg), human PLTP transgenic mice (huPLTPtg) and mice transgenic for both lipid-transfer proteins (huCETPtg/huPLTPtg). These animals showed elevated plasma levels of CETP activity, PLTP activity or both activities, respectively. We evaluated the generation of pre beta-HDL in mouse plasma by immunoblotting and crossed immuno-electrophoresis. Generation of pre beta-HDL was equal in huCETPtg and wild-type mice. In contrast, in huPLTPtg and huCETPtg/huPLTPtg mice, pre beta-HDL generation was 3-fold higher than in plasma from either wild-type or huCETPtg mice. Our findings demonstrate that, of the two plasma lipid-transfer proteins, PLTP rather than CETP is responsible for the generation of pre beta-HDL. These data support the hypothesis of a role for PLTP in the initial stage of reverse cholesterol transport.
Asunto(s)
Proteínas Portadoras/fisiología , Ésteres del Colesterol/metabolismo , Glicoproteínas , Lipoproteínas HDL/biosíntesis , Proteínas de la Membrana/fisiología , Proteínas de Transferencia de Fosfolípidos , Fosfolípidos/metabolismo , Animales , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/sangre , Proteínas de Transferencia de Ésteres de Colesterol , Ésteres del Colesterol/sangre , Lipoproteínas de Alta Densidad Pre-beta , Humanos , Lipasa/sangre , Lípidos/sangre , Lipoproteínas/sangre , Lipoproteínas HDL/metabolismo , Hígado/enzimología , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/sangre , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Fosfolípidos/sangreRESUMEN
We evaluated the hypothesis that plasma cholesteryl ester transfer (CET) and lipase activities are influenced by insulin sensitivity and contribute to the low high-density lipoprotein (HDL) cholesterol observed in type 2 diabetic patients and insulin-resistant non-diabetic subjects. Sixteen type 2 diabetic and 16 non-diabetic subjects participated. Diabetic and non-diabetic subjects were divided in equal groups of eight subjects with low or high insulin sensitivity, which was documented as the glucose infusion rate (M-value) during the last hour of a 3-h euglycaemic hyperinsulinaemic clamp (150 mU kg(-1) h(-1), blood glucose target 4.6 mmol L(-1)). Post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities were measured in samples obtained 1-2 weeks before the clamp. Plasma CET was measured by a radioisotope method. Compared to non-diabetic men with high insulin sensitivity (n = 8) HDL cholesterol was lower in type 2 diabetic men (n=8, p<0.01) and non-diabetic men (n=8, p <0.05) with low insulin sensitivity, and the HDL cholesterylester content was lower in type 2 diabetic men with high insulin sensitivity (n=8, p<0.05). In non-diabetic subjects with high insulin sensitivity, plasma CET was lower than in the other groups (p<0.05 for all). Multiple regression analysis showed that plasma CET (p=0.001) and HL activity (p=0.02) were independently and negatively associated with the M-value. No association between the M-value and LPL activity was observed. Independent negative relationships of HDL cholesterol with plasma CET (p = 0.04) and HL activity (p=0.03) were observed. This study supports the hypothesis that a low HDL cholesterol associated with insulin resistance in type 2 diabetic and non-diabetic subjects is related to a high plasma CET and a high HL activity.
Asunto(s)
Ésteres del Colesterol/sangre , HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Resistencia a la Insulina , Lipasa/sangre , Hígado/enzimología , Adulto , Apolipoproteínas B/sangre , Transporte Biológico , Índice de Masa Corporal , LDL-Colesterol/sangre , VLDL-Colesterol/sangre , Esterificación , Ácidos Grasos no Esterificados/sangre , Hemoglobina Glucada/análisis , Humanos , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
This study examined the role of cholesteryl ester transfer (CET), cholesteryl ester transfer protein (CETP) activity, and phospholipid transfer protein (PLTP) activity in the increased prevalence of coronary artery calcification (CAC) in diabetic subjects compared with nondiabetic subjects and in the loss of the sex difference in CAC in diabetes. CETP activity, PLTP activity, and CET were measured in 195 type 1 diabetic subjects without renal failure and 194 nondiabetic control subjects of similar age (30-55 years) and sex distribution (50% female). CAC was quantified with electron beam computed tomography. CETP activity was higher in diabetic subjects (mean 84 arbitrary units [AU]) than in nondiabetic subjects (80 AU, P = 0.028). PLTP activity was also higher in diabetic subjects (96 AU) than in nondiabetic subjects (81 AU, P < 0.001). However, CET was lower in diabetic men (geometric mean 32 nmol. ml(-1).h(-1)) than nondiabetic men (37 nmol.ml(-1).h(-1), P = 0.004) and did not differ between diabetic (30 nmol. ml(-1).h(-1)) and nondiabetic (32 nmol.ml(-1).h(-1), P = 0.3) women. CETP and PLTP activities were not associated with CAC. CET was positively associated with CAC in both diabetic and nondiabetic subjects (odds ratio per 10 nmol.ml(-1).h(-1) increase in CET in all subjects = 1.4, P = 0.001). The prevalence of CAC was similar in diabetic (51%) and nondiabetic (54%, P = 0.7) men but was much higher in diabetic (47%) than nondiabetic (21%, odds ratio 3.6, P < 0.001) women so that there was no sex difference in CAC in diabetic subjects. The odds of CAC in diabetic women compared with nondiabetic women was altered little by adjustment for CETP activity, PLTP activity, or CET (odds ratio on adjustment 3.7, P < 0.001). The greater effect of diabetes on CAC in women than in men, i.e., the loss of the sex difference in CAC, was independent of CETP and PLTP activity and CET. In conclusion, among both diabetic and nondiabetic subjects, higher cholesteryl ester transfer is a risk factor for CAC. However, abnormalities in cholesteryl ester transfer or lipid transfer protein activities do not underlie the increased CAC risk in diabetic women compared with nondiabetic women or the loss of the sex difference in CAC in diabetes.
Asunto(s)
Calcinosis/etiología , Proteínas Portadoras/sangre , Ésteres del Colesterol/metabolismo , Enfermedad Coronaria/etiología , Diabetes Mellitus Tipo 1/sangre , Angiopatías Diabéticas/etiología , Glicoproteínas , Proteínas de la Membrana/sangre , Proteínas de Transferencia de Fosfolípidos , Adulto , Proteínas de Transferencia de Ésteres de Colesterol , Estudios Transversales , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Humanos , Lipoproteínas/sangre , Masculino , Persona de Mediana Edad , Valores de Referencia , Caracteres SexualesAsunto(s)
Colesterol/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Losartán/uso terapéutico , Adulto , Albuminuria , Antagonistas de Receptores de Angiotensina , LDL-Colesterol/sangre , VLDL-Colesterol/sangre , Diabetes Mellitus Tipo 1/orina , Humanos , Persona de Mediana EdadRESUMEN
OBJECTIVES: To determine the long-term effects of unfiltered coffee consumption on the activity levels of cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP) and lecithin:cholesterol acyltransferase (LCAT) and to assess a possible role of CETP activity levels in the rise in serum LDL cholesterol. SUBJECTS AND DESIGN: Forty-six healthy normolipidaemic subjects consumed 0.9 L of either French-press or filtered coffee for 24 weeks. Fasting blood samples were obtained after 0, 2, 12 and 24 weeks of intervention and after and 12 weeks of follow-up. MAIN OUTCOME MEASURES: Serum activity levels of CETP, PLTP and LCAT. RESULTS: Relative to baseline, French-press coffee significantly increased average CETP activity by 12% after 2 weeks, by 18% after 12 weeks, and by 9% after 24 weeks. PLTP activity was significantly increased by 10% after 12 and 24 weeks. LCAT activity was significantly decreased by 6% after 12 weeks and by 7% after 24 weeks. The increase in CETP clearly preceded the increase in LDL cholesterol, but not the increase in total triglycerides. However, consumption of French-press coffee caused a persistent rise in CETP activity, whereas the rise in serum triglycerides was transient. CONCLUSIONS: Consumption of cafestol and kahweol cause a long-term increase in CETP as well as PLTP activity; the increase in CETP activity may contribute to the rise in LDL cholesterol.
Asunto(s)
Proteínas Portadoras/sangre , LDL-Colesterol/sangre , Diterpenos/efectos adversos , Glicoproteínas , Proteínas de Transferencia de Fosfolípidos , Adulto , Anciano , Proteínas de Transferencia de Ésteres de Colesterol , Café/efectos adversos , Femenino , Humanos , Masculino , Proteínas de la Membrana/sangre , Persona de Mediana Edad , Fosfatidilcolina-Esterol O-Aciltransferasa/sangreRESUMEN
Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Part of this inverse association may be explained by its effects on HDL. Paraoxonase, an HDL-associated enzyme, has been suggested to protect against LDL oxidation. We examined the effects of moderate consumption of red wine, beer and spirits in comparison with mineral water on paraoxonase activity in serum. In this diet-controlled, randomised, cross-over study 11 healthy middle-aged men consumed each of the beverages with evening dinner for 3 weeks. At the end of each 3 week period, blood samples were collected pre- and postprandially and after an overnight fast. Fasting paraoxonase activity was higher after intake of wine (P<0. 001), beer (P<0.001), and spirits (P<0.001) than after water consumption (149.4+/-111.1, 152.6+/-113.1, 152.8+/-116.5 and 143. 1+/-107.9 U/l serum), but did not differ significantly between the 3 alcoholic beverages. Similar effects were observed pre- and postprandially. The increases in paraoxonase activity were strongly correlated with coincident increases in concentrations of HDL-C and apo A-I (r=0.60, P<0.05 and r=0.70, P<0.05). These data suggest that increased serum paraoxonase may be one of the biological mechanisms underlying the reduced coronary heart disease risk in moderate alcohol consumers
Asunto(s)
Consumo de Bebidas Alcohólicas , Enfermedad Coronaria/prevención & control , Dieta , Esterasas/sangre , Lipoproteínas HDL/metabolismo , Adulto , Apolipoproteínas A/metabolismo , Arildialquilfosfatasa , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/metabolismo , Estudios Cruzados , Humanos , Lipoproteínas HDL/sangre , Masculino , Persona de Mediana Edad , Valores de Referencia , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Plasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high-density lipoproteins (HDLs) towards apolipoprotein (apo) B-containing lipoproteins are key steps in HDL metabolism. MATERIALS AND METHODS: The effects of exogenous hyperinsulinaemia on plasma CET and EST, measured with isotope methods, were evaluated in 10 male normotriglyceridaemic (plasma triglycerides <2.0 mmol L-1) patients with type 2 diabetes and 10 individually matched healthy subjects during a two-step hyperinsulinaemic euglycaemic clamp over 6-7 h. RESULTS: No between-group differences in baseline plasma lipid parameters were observed, but the HDL cholesteryl ester content was lower (P < 0.02) and the HDL triglyceride content was higher (P < 0.05) in diabetic patients. Baseline CET and EST were similar in the groups. In both groups, hyperinsulinaemia decreased plasma triglycerides (P < 0.01) and the HDL triglyceride content (P < 0.01) compared with saline infusion in healthy subjects, whereas the HDL cholesteryl ester content increased (P < 0.05 vs. saline infusion) in diabetic patients. CET was similarly decreased by hyperinsulinaemia in both groups (P < 0.01 vs. saline infusion). In contrast, the change in EST in either group was not different from that during saline administration. In the combined group, baseline CET was positively correlated with plasma triglycerides (Rs = 0.68, P < 0.01). The HDL cholesteryl ester content was negatively (Rs = -0.48, P < 0.05) and the HDL triglyceride content was positively (Rs = 0.64, P < 0.01) correlated with CET. CONCLUSION: Insulin infusion decreases plasma CET in conjunction with a fall in triglycerides but does not decrease cholesterol esterification in healthy and type 2 diabetic subjects, indicating that acute hyperinsulinaemia has a different effect on these processes involved in HDL metabolism. Despite unaltered fasting plasma CET, HDL core lipid composition was abnormal in diabetic patients, suggesting that additional mechanisms may contribute to changes in HDL metabolism in diabetes mellitus.
Asunto(s)
Ésteres del Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glicoproteínas , Insulina/farmacología , Apolipoproteínas B/sangre , Transporte Biológico Activo/efectos de los fármacos , Proteínas Portadoras/sangre , Estudios de Casos y Controles , Proteínas de Transferencia de Ésteres de Colesterol , Humanos , Lipoproteínas HDL/sangre , Masculino , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
Dietary fats are known to influence the fatty acid profile of plasma lipids, including phospholipids which are substrates of lecithin:cholesterol acyltransferase (LCAT; EC 2.3.1.43), an important enzyme in lipoprotein metabolism. We tested whether the dietary fatty acid profile has an effect on LCAT activity in an animal model. Rats were conditioned to eat two meals per day, which were enriched in either palmitic, oleic or linoleic acids, for 10 weeks. Serum was isolated from blood samples taken prior to the meal. The LCAT activity was determined in two ways: (1) by measuring serum cholesterol esterification rates, which are an estimate of LCAT action on endogenous lipoproteins, and (2) by measuring serum LCAT activity levels with excess exogenous substrates, an estimate of LCAT mass. Animals receiving the linoleic acid diet had lower serum concentrations of unesterified cholesterol and triglycerides, if compared with animals fed oleic acid or palmitic acid diets (p < 0.05). Serum LCAT activity levels (measured with excess exogenous substrates) were not different, but both the absolute and fractional rates of cholesterol esterification were highest on the linoleic acid rich diet (p < 0.01), showing that LCAT action on endogenous lipoproteins is improved. No differences were found in serum apolipoprotein B and A-IV concentrations between the dietary groups. Apolipoprotein A-I levels were lowest in the palmitic acid group (oleic and linoleic > palmitic; p < 0.05), and apolipoprotein E levels were highest in the palmitic acid group (palmitic > oleic and linoleic; p < 0.05). It is concluded that a linoleic acid rich diet may cause increased metabolism of serum cholesterol by LCAT in rats. This effect is not due to elevated serum concentrations of LCAT or of its apolipoprotein activators, but most likely to changes in the chemical composition of endogenous lipoprotein substrates. It remains to be established whether the serum cholesterol esterification rates measured in vitro are related to in vivo rates of reverse cholesterol transport.
Asunto(s)
Alimentación Animal , Ésteres del Colesterol/sangre , Grasas de la Dieta/administración & dosificación , Ácido Linoleico/administración & dosificación , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Animales , Peso Corporal , Lípidos/sangre , Masculino , Ácido Oléico/administración & dosificación , Ácido Palmítico/administración & dosificación , Ratas , Ratas Wistar , Triglicéridos/sangreRESUMEN
We have previously reported that normolipidemic smokers are lipid intolerant due to increased responses of triglyceride-rich lipoproteins (TRL) apolipoprotein B-48, triglyceride (TG), and retinyl esters to a mixed meal compared to non-smokers. To investigate whether postprandial high density lipoprotein (HDL), apolipoprotein A-I (apoA-I), apolipoprotein A-II (apoA-II), and apolipoprotein E (apoE) concentrations or lipid transfer protein activities are affected by cigarette smoking, we investigated 12 male smokers and 12 non-smokers with comparable fasting lipoprotein profile, BMI, and age. Plasma samples obtained after an overnight fast and postprandially were separated by density gradient ultracentrifugation. Postprandial apoA-I, lipoprotein AI-particles (LpA-I), HDL-cholesterol, and HDL apoE concentrations decreased in smokers, but remained unchanged in controls. Concomitantly, cholesterol and apoE concentrations increased significantly in TRL fractions in smokers. Fasting lecithin:cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) activity levels, as well as esterification rates (EST) and phospholipid transfer rates were comparable between the groups. Cholesteryl ester transfer protein (CETP) activity levels were lower in the smokers. Postprandially EST increased, but CETP and PLTP activities deceased in smokers as compared to controls. We conclude, that even healthy, normolipidemic smokers have altered postprandial high density lipoprotein (HDL) cholesterol and apolipoprotein composition, as well as lipid transfer protein activities. The shift of cholesterol and apoE from HDL to the triglyceride-rich lipoprotein (TRL) fraction, together with decreased plasma apoA-I and LpA-I concentrations during alimentary lipemia may indicate impaired reverse cholesterol transport. Both the postprandial increase in TRL and the lowering of HDL may promote atherogenesis in smokers.
Asunto(s)
Apolipoproteína A-I/sangre , Apolipoproteínas E/sangre , Proteínas Portadoras/sangre , HDL-Colesterol/sangre , Colesterol/sangre , Glicoproteínas , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Periodo Posprandial , Fumar/sangre , Adulto , Glucemia/análisis , Péptido C/sangre , Proteínas de Transferencia de Ésteres de Colesterol , Ésteres del Colesterol/sangre , Grasas de la Dieta , Humanos , Insulina/sangre , Lipoproteínas VLDL/sangre , Masculino , Valores de Referencia , Factores de TiempoRESUMEN
We studied the effect of a single oral fat load, supplemented with retinyl palmitate (RP), on high density lipoprotein (HDL) lipids in six normolipidemic men with coronary artery disease (CAD) and in six age- and lipid-matched controls. All subjects were selected from a study group which underwent the same protocol 2 years earlier. Post-prandial total plasma lipids, plasma RP levels, and HDL lipids were evaluated at 2-h intervals up till 10 h after the meal. In most subjects the post-prandial response of plasma triglyceride (TG) and plasma RP was identical in the first and second tests. Following the fat load, control subjects showed no change in HDL total cholesterol (TC) or HDL cholesteryl ester (CE) and showed an increase in HDL-TG. CAD subjects however showed a decrease in HDL-TC and HDL-CE and an increase in HDL-TG, similar to the increase in control subjects. In control subjects an increase in HDL phospholipid (PL) was apparent between 0 and 8 h after the fat load. By contrast, in CAD subjects the increase in HDL-PL was only found after as long as 6 h. The magnitude of the post-prandial response of HDL-PL measured during the test was significantly lower in the CAD group. The effects of the fat load on HDL free cholesterol (FC) were similar to the changes in HDL-PL. These data support the hypothesis that PL and FC released during the degradation of chylomicrons as surface remnants are taken up by HDL. This process is clearly delayed in normolipidemic CAD subjects compared with controls. The data suggest that differences in the post-prandial response to an oral fat load in normolipidemic CAD patients and control subjects are not confined to the clearance of TG-rich lipoproteins, but also involve a difference in the uptake of chylomicron surface material by HDL.
Asunto(s)
HDL-Colesterol/sangre , Enfermedad Coronaria/sangre , Grasas de la Dieta/administración & dosificación , Glicoproteínas , Fosfolípidos/sangre , Periodo Posprandial , Adulto , Anciano , Proteínas Portadoras/sangre , Proteínas de Transferencia de Ésteres de Colesterol , Cromatografía Líquida de Alta Presión , Diterpenos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Ésteres de Retinilo , Triglicéridos/sangre , Vitamina A/administración & dosificación , Vitamina A/análogos & derivadosRESUMEN
We measured the effects of consumption of moderate amounts of beer, wine or spirits with evening dinner on plasma LDL and HDL levels as well as composition in 11 healthy middle-aged men. Forty grams of alcohol were consumed daily with dinner for a period of 3 weeks. Mineral water was used as a negative control. Dinner was served at 6 pm and blood samples were obtained at 1 h before and 3, 5, 9, and 13 h after the start of the meal. No differences were detected between the effects of the different alcohol-containing beverages. Plasma levels of triglycerides (TG), measured 1 h before dinner were very variable and higher than fasting values (means of 2.2 and 1.5 mM, respectively). Daily consumption of 40 g of alcohol with dinner resulted in increased postprandial plasma TG levels and decreased low density lipoprotein (LDL) cholesterol concentrations. These effects were transient and observed at 11 pm (TG) and 9 pm and 11 pm (LDL). In contrast, high density lipoproteins (HDL) were raised by alcohol intake at all time points analysed. HDL composition was changed by alcohol consumption, resulting in a raised HDL-cholesterol/apo A-I ratio at 5 pm and 9 pm. The observed alcohol-dependent effects on plasma HDL and LDL during the postprandial phase are considered anti-atherogenic and may contribute to the observed protection against coronary heart disease by moderate alcohol consumption.
Asunto(s)
Consumo de Bebidas Alcohólicas , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Adulto , Arteriosclerosis/prevención & control , Etanol/farmacología , Humanos , Masculino , Persona de Mediana Edad , Periodo PosprandialRESUMEN
Cafestol and kahweol-diterpenes present in unfiltered coffee-strongly raise serum VLDL and LDL cholesterol and slightly reduce HDL cholesterol in humans. The mechanism of action is unknown. We determined whether the coffee diterpenes may affect lipoprotein metabolism via effects on lipid transfer proteins and lecithin:cholesterol acyltransferase in a randomized, double-blind cross-over study with 10 healthy male volunteers. Either cafestol (61-64 mg/day) or a mixture of cafestol (60 mg/day) and kahweol (48-54 mg/day) was given for 28 days. Serum activity levels of cholesterylester transfer protein, phospholipid transfer protein and lecithin:cholesterol acyltransferase were measured using exogenous substrate assays. Relative to baseline values, cafestol raised the mean (+/- S.D.) activity of cholesterylester transfer protein by 18 +/- 12% and of phospholipid transfer protein by 21 +/- 14% (both P < 0.001). Relative to cafestol alone, kahweol had no significant additional effects Lecithin:cholesterol acyltransferase activity was reduced by 11 +/- 12% by cafestol plus kahweol (P = 0.02). It is concluded that the effects of coffee diterpenes on plasma lipoproteins may be connected with changes in serum activity levels of lipid transfer proteins.
Asunto(s)
Proteínas Portadoras/sangre , Diterpenos/administración & dosificación , Adulto , Café/efectos adversos , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , MasculinoRESUMEN
Lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are important factors involved in HDL metabolism. Altered plasma activity levels of these factors could play a role in the increase in high density lipoprotein (HDL) cholesterol associated with moderate alcohol consumption. We measured plasma LCAT, CETP and PLTP activities with exogenous substrate assays, as well as lipoproteins and HDL lipids in 6 alcohol-abstaining men, 18 matched men who used < or = 1 and 18 men who used > or = 1 alcohol-containing drinks per day. Plasma cholesterol and triglycerides were similar in the three groups. HDL total cholesterol, HDL cholesteryl ester, HDL free cholesterol and HDL triglycerides were higher in the alcohol drinkers compared to the abstainers (all P < 0.05). No differences in plasma LCAT, CETP and PLTP activity levels were observed between the three groups. Analysis of covariance also demonstrated that the use of alcohol was associated with higher HDL cholesterol (P < 0.04), whereas plasma LCAT, CETP and PLTP activity levels were not related to alcohol consumption. Furthermore, HDL cholesteryl ester was positively associated with LCAT activity (P < 0.001), PLTP activity (P < 0.01) and alcohol intake (P < 0.04) and negatively with plasma triglycerides (P < 0.001) and CETP activity (P < 0.03); indicating that alcohol influenced HDL cholesteryl ester independently from these biochemical parameters. The higher HDL cholesterol associated with moderate alcohol consumption is, therefore, unlikely to be caused by and effect on plasma LCAT, CETP or PLTP activity levels.
Asunto(s)
Consumo de Bebidas Alcohólicas/sangre , Proteínas Portadoras/sangre , HDL-Colesterol/sangre , Fosfatidilcolina-Esterol O-Aciltransferasa/sangre , Adolescente , Adulto , Anciano , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We determined the effects of different dialysis conditions on the antioxidant content, duration of the lag phase and oxidation rate of LDL. Dialysis for 22 h resulted in a 56%--66% reduction in the concentrations of beta-carotene, lycopene and alpha-tocopherol. The lag phase of copper-induced oxidation of freshly isolated LDL was considerably longer than that of LDL dialysed for 22 or 44 h. Our data show that dialysis may result in LDL preparations with antioxidant compositions that are not truly representative of freshly isolated lipoproteins.
Asunto(s)
Antioxidantes/análisis , Diálisis , Lipoproteínas LDL/química , Adulto , Análisis de Varianza , Ácido Edético , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidación-ReducciónRESUMEN
Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Alcohol may exert protection through its effects on the metabolism of plasma lipoproteins. In the present study we investigated the effects of moderate wine consumption with an evening dinner on lipoprotein composition and parameters of reverse cholesterol transport (plasma lipid transfer reactions and cholesterol esterification) in eight healthy middle-aged men. Wine consumption, if compared with mineral water, resulted in increased postprandial plasma levels of triglyceride-(TG)-rich lipoproteins (P < 0.005 or < 0.002 at two different time points) and in increased net mass transfer of cholesterylesters (CE) from high-density lipoprotein (HDL) to apolipoprotein B-containing lipoproteins during in vitro incubation of plasma (P < 0.001). Net mass transfer of TG (in the opposite direction) was also significantly increased by wine (P = 0.014). The concentrations of total plasma cholesterol, HDL-cholesterol and apolipoproteins A-I, A-II and B did not change postprandially and were not affected significantly by wine, but the CE TG-1 in HDL was affected postprandially and decreased by wine consumption. It is concluded that moderate wine consumption with evening dinner induces transfer reactions of CE and TG between HDL and TG-rich lipoproteins. Due to the fact that wine raises plasma TG, it also causes changes in plasma cholesterol metabolism and lipoprotein composition, without major effects on total plasma cholesterol concentration.
Asunto(s)
Consumo de Bebidas Alcohólicas , Glicoproteínas , Lípidos/sangre , Proteínas Portadoras/sangre , Proteínas de Transferencia de Ésteres de Colesterol , Ésteres del Colesterol/sangre , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas VLDL/sangre , Masculino , Persona de Mediana Edad , Triglicéridos/sangre , VinoRESUMEN
The average diet may provide some 8-10 g/day of unsaturated fatty acids with a trans double bond. Previous studies showed that dietary trans fatty acids may simultaneously raise low-density lipoprotein (LDL) cholesterol and reduce high-density lipoprotein (HDL) cholesterol. Human plasma contains a protein (CETP) which transfers cholesterylesters from HDL to lipoproteins of lower density. We hypothesized that CETP could play a role in the effect of trans fatty acids on lipoproteins and measured the activity levels of CETP in serum samples from a 9-week study in which 55 volunteers were fed three controlled diets with different fatty acid profiles. Mean activity was 114 (% of reference serum) after consumption of a high trans fatty acid diet, as opposed to 96 after linoleic acid and 97 after stearic acid (P < 0.02). We conclude that the increased activity of CETP may contribute to the rise in LDL cholesterol and the fall in HDL cholesterol seen on diets with high contents of trans fatty acids.
Asunto(s)
Proteínas Portadoras/sangre , Grasas de la Dieta/farmacología , Ácidos Grasos Insaturados/farmacología , Glicoproteínas , Análisis de Varianza , Proteínas Portadoras/efectos de los fármacos , Proteínas de Transferencia de Ésteres de Colesterol , Ésteres del Colesterol/sangre , Femenino , Humanos , Ácido Linoleico , Ácidos Linoleicos/farmacología , Masculino , Valores de Referencia , Caracteres Sexuales , Ácidos Esteáricos/farmacología , Factores de TiempoRESUMEN
Albumin is an acceptor of lysophosphatidylcholine (LPC), product of the lecithin:cholesterol acyl transferase (LCAT) reaction, and it has been suggested that low LCAT activity and reduced cholesterol esterification rate in patients with the nephrotic syndrome may be linked to depletion of albumin. Effects of low plasma albumin levels on LCAT activity, cholesterol esterification rates and LPC-binding were therefore studied in hyperlipidemic nephrotic (NS) and analbuminemic (NAR) rats. LPC-binding was also measured in normoalbuminemic rats with dietary hypercholesterolemia. Remarkably, LCAT activity, measured with excess exogenous substrate, was not decreased but increased in both NAR and NS rats. Molar esterification rates with endogenous substrate were increased in NAR but normal in NS rats. In normoalbuminemic rats, with or without hypercholesterolemia, LPC was primarily found in the lipoprotein-deficient plasma and the HDL3 fraction. In NAR and NS rats LPC levels were increased in lipoproteins (notably in LDL and HDL2), but, in marked contrast to normoalbuminemic rats, decreased in lipoprotein-deficient plasma. Phosphatidylcholine, quantitatively the major phospholipid, was distributed proportionally over the lipoproteins in NS, NAR and control rats. Therefore, in hypoalbuminemia and analbuminemia LPC is mainly bound to lipoproteins, which is in contrast to the paucity of LPC in these particles in normoalbuminemic rats. Cholesterol esterification in nephrotic plasma is thus not impaired by lack of an acceptor for LPC-binding. The absence of an increase in molar cholesterol esterification in conjunction with increased LCAT activity points to a possible defect of the substrate for this reaction in nephrotic plasma. Increased LPC levels in LDL, a characteristic of oxidized LDL, may be a hitherto unrecognized atherosclerotic risk factor in the nephrotic syndrome.