Moderately elevated plasma/serum triglycerides (2 -10 m mol/l) signalize increased risk for cardiovascular disease or presence of non- alcoholic steatohepatitis. Extremely elevated triglycerides (more than 10 mmol/l) signalize increased risk for pancreatitis and lipemia retinalis. The concentration of triglycerides is regulated by many genetic and nongenetic factors. Extremely elevated triglycerides not provoked by nutritional factors, especially inappropriate alcohol intake are more likely to have a monogenic cause. On the contrary, mildly to moderately elevated triglycerides are often caused by polygenic disorders; these could be also associated with central obesity, insulin resistance, and diabetes mellitus. Concentration of triglycerides is also closely interconnected with presence of atherogenic remnant lipop roteins, impaired reverse cholesterol transport and more atherogenic small LDL particles. In general, there is tight association between triglycerides and many other metabolic factors including intermediate products of lipoprotein metabolism which are freq uently atherogenic. Therefore, reliable evaluation of the independent role of triglycerides especially in atherosclerosis and cardiovascular disease is difficult. In individual cases values of HDL cholesterol, non -HDL cholesterol (total minus HDL cholester ol), non -HDL/nonLDL cholesterol (total minus HDL minus LDL cholesterol, especially in nonfasting status), atherogenic index of plasma and/or apolipoprotein B could help in decisions regarding a ggressiv eness of treatment., J. Piťha, J. Kovář, T. Blahová., and Obsahuje bibliografii
Lipoprotein lipase (LPL) is a key factor determining the clearance of triglycerides from the circulation. The enzyme activity is tissue-specifically regulated by insulin, but it is not clear yet how insulin regulates the total LPL activity in the circulation. To answer such question, we measured LPL activity using the intravenous fat tolerance test (IVFTT) that was carried out 1 h before as well as 2 h and 4 h after oral administration of glucose (75 g) in eleven healthy male volunteers. In control experiments, no glucose was given to the subjects. Glucose administration resulted in an expected increase in plasma glucose and insulin and in a suppression of non-esterified fatty acid concentration. The LPL activity assessed in IVFTT as a k2 rate constant did not change in control experiments and decreased to 78 % and 73 % of baseline values 2 h and 4 h after glucose administration, respectively (p=0.01). Similarly, LPL activity measured in the plasma after intravenous injection of heparin at the end of the experiments was 16 % lower (p<0.05) after glucose administration. In conclusion, LPL activity is already downregulated in vivo 2 h after glucose administration. The results of our study indicate that repeated IVFTT is a promising approach for studying acute changes in LPL activity., E. Jindřichová, S. Kratochvílová, J. Kovář., and Obsahuje bibliografii a bibliografické odkazy
Imprinting of an increased sensitivity to a high-fat, high cholesterol (HFHC) diet by dietary manipulation in early life was studied in two strains of rat, i.e. in Prague hereditary hypercholesterolaemic rats (PHHC) and Wistar rats, from which the PHHC strain was obtained by selection and inbreeding. Whereas no effect of early life nutrition on cholesterolaemia induced by HFHC diet was found in control Wistar rats, significant imprinting of increased sensitivity to the same diet was demonstrated in PHHC rats. This imprinting increased the concentration of apoB- containing lipoprotein and liver cholesterol concentration in animals fed HFHC diet for a period of two months after weaning. No effect of this imprinting on endogenous cholesterol synthesis could be demonstrated. It is concluded that imprinting of increased sensitivity to HFHC diet by dietary manipulation in early life is not a general phenomenon but depends on underlying genetic predisposition(s).
Lipoprotein (a) [Lp(a)] is an LDL-like particle that contains an apolipoprotein B100 molecule covalently bound to a plasminogen-like glycoprotein, apolipoprotein (a) [apo(a)]. Epidemiological evidence supports a direct and causal association between Lp(a) levels and coronary risk. On the contrary, a few prospective findings demonstrate inverse association of Lp(a) levels with risk of type 2 diabetes (T2DM). The aim of our study was to evaluate the association of Lp(a) with indicators of insulin resistance (IR) and metabolic syndrome (MS), which precede development of T2DM. We enrolled 607 asymptomatic dyslipidemic subjects (295 men and 312 women, mea n age 45.6±14.0 years) into our cross-sectional study. Lp(a) concentrations correlated inversely with TG, AIP, insulin, HOMA, C-peptide, BMI, waist circumference, and number of MS components (p<0.01 for all). Subjects with MS had significantly lower Lp(a) concentrations in comparison with those without the presence of this phenotype (p<0.0001). Serum concentrations of Lp(a) in the lower (1th 3rd) quartiles of insulin and HOMA were significantly higher than in the 4 th quartile of these insulin resistance markers (p<0.001). Odds ratios of having increased markers of IR (TG, HOMA) and MS in top quartile of Lp(a) also indicate inverse association of Lp(a) with IR. The results of our study support an inverse association of Lp(a) levels with IR and MS that precedes overt T2DM diagnosis., H. Vaverková, D. Karásek, M. Halenka, L. Cibíčková, V. Kubíčková., and Obsahuje bibliografii
HDL cholesterol resp. apolipoprotein A1 concentrations are tools to estimate individual CVD risk, although only a part of HDL particles participate in reverse cholesterol transport (RCT). This discrepancy was analyzed in life style change based on increase of physical activity and dietary counseling. Efflux of cholesterol from pre-labeled macrophages to plasma acceptors of tested individuals was used as an RCT measure. Changes of lipoprotein parameters, glucose, fasting insulin concentrations and RCT were analyzed in 15 obese women after 9-week intervention consisted of 5 sessions of increased physical activity per week. Controlled increase in physical activity for 9 weeks induced a decrease of body weight averaging 9 kg (ranged from 2.3 to 15.5 kg). The intervention leads to significant decreases of triglycerides, apoprotein A1 and apoprotein B concentration, whereas total cholesterol, LDL cholesterol and HDL cholesterol did not change significantly. The increase of RCT was not significant, but there was highly significant negative correlation between individual decrease of body weight and an increase of RCT. Significant increase of RCT was found in 13 persons with a weight reduction more than 3.5 kg. Substantial weight loss is necessary to increase RCT., I. Králová Lesná ... [et al.]., and Obsahuje seznam literatury
The apolipoprotein A-V (apo A-V) plays an important role in regulation of triglyceride (TG) concentration in serum. To better understand how apo A-V affects triglyceridemia and glucoregulation, the lipoprotein lipase (LPL) activity was determined using intravenous fat tolerance test (IVFTT) and oral glucose tolerance test (oGTT) was performed in carriers of apolipoprotein A-V gene ( APOAV) variants known to be associated with increased triglyceridemia. Twelve carriers of 19W variant, 16 carriers of -1131C variant, 1 combined heterozygote and 16 control subjects homozygous for wild type variants (19S/-1131T) were selected from a population sample and matched with respect to body mass index and age. The APOAV variants carriers had increased TG, very low density lipoprotein-TG, and apo B concentrations (p < 0.05). The LPL activity evaluated as k2 rate constant for clearance of Intralipid® was 14 % lower in APOAV variants carriers. The depression of nonesterified fatty acids (NEFA) concentration after glucose load was delayed in APOAV variants carriers in spite of the same insulinemia and glycemia. Our results suggest that variants of APOAV combined with increased triglyceridemia are associated with lower LPL activity in vivo and with disturbances of regulation of NEFA concentration after glucose load., J. Kovář, V. Adámková., and Obsahuje bibliografii a bibliografické odkazy
Lipoprotein(a) [Lp(a)] comprises of an LDL particle and apolipoprotein(a) [apo(a)] and its elevated levels are considered a risk factor for atherosclerosis. The aim of our study was to find out whether elevated Lp(a) levels are associated with increased risk of atherosclerosis in patients with multiple other risk factors. We further tested the association of three polymorphisms of the apo(a) gene promoter with Lp(a) levels. No significant correlation was detected between Lp(a) levels and lipid and clinical parameters tested. The study demonstrated a significantly (p=0.0219) elevated Lp(a) level (mean 28±35 mg/dl, median 0.14) in patients with coronary heart disease (CHD). In a group with premature CHD the correlation was not significant anymore. There was a significant correlation between polymorphic loci of the promoter region of apo(a) gene and Lp(a) levels (+93C>T, p=0.0166, STR, p<0.0001). Our study suggests that elevated Lp(a) level is an independent risk factor of CHD in carriers of other important CHD risk factors. Observed association of sequence variants of the promoter of apo(a) gene with Lp(a) levels is caused in part due to linkage to a restricted range of apo(a) gene length isoforms., L. Zlatohlávek, K, Zídková, M. Vrablík, T. Haas, M. Prusíková, H. Svobodová, R. Češka., and Obsahuje bibliografii a bibliografické odkazy
It is well known that the consumption of moderate doses of alcohol leads to the increase of HDL-cholesterol (HDL-C). Atheroprotectivity of HDL particles is based primarily on their role in reverse cholesterol transport (RCT). In the study with a crossover design 13 male volunteers were studied in two different regimens: i) drinking of 36 g alcohol daily and ii) drinking only non-alcoholic beverages, to test whether alcohol-induced increase of HDL cholesterol can affect cholesterol efflux (CHE) from cell culture of labeled human macrophages. Alcohol consumption induced significant (p<0.05) increases of HDL cholesterol from 1.25±0.32 to 1.34±0.38 mmol/l and Apo A1 from 1.34±0.16 to 1.44±0.19 g/l. These changes were combined with a slight increase of cholesterol efflux from 13.8±2.15 to 14.9±1.85 % (p=0.059). There were significant correlations between individual changes of HDL-C and Apo A1 concentrations and individual changes of CHE (0.51 and 0.60, respectively). In conclusion, moderate alcohol consumption changes the capacity of plasma to induce CHE only at a border line significance., I. Králová Lesná ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The review aims to summarize current knowledge on the effects of moderate alcohol consumption ( 1 standard drink a day for women; 2 drinks a day for men) on triglyceride concentration in circulation. Current evidence suggests that the relationship between alcohol consumption and triglyceridemia is J -shaped. Triglyceridemia is lowest in subjects who drink 10 -20 g/alcohol a day. Such a J -shaped association is comparable with that described for the relationship between alcohol and cardiovascular risk. On the contrary, alcohol taken with a meal increases and prolongs postprandi al triglyceridemia. Such effects of alcohol consumption may be at least partially explained by the effects of ethanol on lipoprotein lipase (LPL) activity. Long -term moderate alcohol consumption increases LPL activity, which may explain its TG -lowering effect. On the other hand, LPL activity is acutely downregulated by ethanol, which explains increased postprandial triglyceridemia., J. Kovář, K. Zemánková., and Obsahuje bibliografii