The Srb1+1050T allele is associated with metabolic syndrome in children but not with cholesteryl ester plasma concentrations of high-density lipoprotein subclasses.

BACKGROUND: Low cholesterol and phospholipid plasma levels of some high-density lipoprotein (HDL) subclasses have been described in children with metabolic syndrome. Scavenger receptor class B type I (SR-BI) has been proposed to be at the origin of such HDL alterations because of its key role on cholesteryl esters-HDL metabolism. However, the possible contribution of SR-BI has not been specifically explored in this kind of patients. METHODS: Plasma lipid concentrations of HDL subclasses, i.e., triglycerides (TG), phosphatidylcholine (Ph), free cholesterol (FC), and total cholesterol (TC), were determined by enzymatic staining on polyacrylamide gradient gels (PAGE) in 39 pediatric patients with metabolic syndrome and 65 children as controls. Cholesteryl esters were estimated by the difference between TC and FC. Proteins of HDL subclasses were also stained for the assessment of the relative size distribution of HDL. For statistical analysis, the study population was grouped by Srb1 +1050C-->T polymorphism (rs5888) as carriers or noncarriers of the T allele, and data were corrected by metabolic syndrome status. RESULTS: The Srb1 +1050T allele was associated with metabolic syndrome [odds ratio (OR)=2.18 (1.12-4.22), P=0.02]. Plasma TG corresponding to HDL3a, as well as the relative proportion of this HDL subclass, were slightly higher in carriers of the T allele as compared to CC homozygous subjects. Cholesteryl esters plasma concentrations of all HDL subclasses were comparable between T allele carriers and noncarriers after correction by metabolic syndrome status. CONCLUSIONS: Srb1 +1050T was associated with metabolic syndrome, but T carrier subjects did not show important differences concerning HDL subclasses as compared to noncarriers.

Lipid plasma concentrations of HDL subclasses determined by enzymatic staining on polyacrylamide electrophoresis gels in children with metabolic syndrome.

BACKGROUND: The antiatherogenic role of different HDL subclasses is still controversial. HDL particles of the same size can have different lipid contents in some physiopathological situations. However, little is known about the plasma lipid levels of HDL subclasses when they are separated by their hydrodynamic diameter. METHODS: Triglycerides (Tg), phosphatidylcholine (Ph), and cholesterol (C) plasma concentrations of HDL subclasses, were determined by enzymatic staining on polyacrylamide gradient gel (PAGE) in 50 pediatric patients with metabolic syndrome (MS), and 50 control children paired by age and gender. Proteins of HDL subclasses were also stained for the assessment of the relative size distribution of HDL. RESULTS: Relative HDL size distribution was shifted to small particles in MS pediatric patients when determined per protein. In contrast, cholesterol plasma concentrations corresponding to the HDL2b, 2a, 3a, and 3b subclasses were decreased; triglycerides of HDL3b and 3c, as well as plasma phospholipids from HDL3c, were elevated in MS patients as compared to controls. The C-to-Ph ratio, considered as indicative of HDL composition, was similar among the 5 HDL subclasses in control subjects, whereas this ratio gradually decreased from large HDL2b to small HDL3c in the MS group. Cholesterol plasma concentrations of HDL subclasses correlated with the components of the MS. CONCLUSIONS: Lipids of HDL subclasses provide more and accurate information than the relative HDL size distribution determined by protein staining, and may contribute to understand better HDL metabolism and the coronary risk associated to these lipoproteins.

Pioglitazone increases the fractional catabolic and production rates of high-density lipoproteins apo AI in the New Zealand White Rabbit.

Pioglitazone is an agonist of the peroxisome proliferator-activated receptor gamma (PPARgamma) that raises HDL-cholesterol plasma in humans. Whether pioglitazone-mediated modifications in HDL-apolipoprotein AI (apo AI) turnover in vivo contribute to this effect has not been completely elucidated. Therefore, we performed kinetic studies of HDL-apo AI radiolabeled with 125I in male New Zealand White rabbits after 6 weeks of 0.6 (n = 8), 1.75 (n = 8), and 2.6 mg/kg/day (n = 7) pioglitazone and vehicle (n = 12) treatment. Fractional catabolic rate (FCR) of HDL-apo AI was significantly higher in 1.75 and 2.6 mg/kg pioglitazone-treated animals, as compared with control rabbits (0.057+/-0.014 and 0.049+/-0.01 versus 0.025+/-0.005 pools/h, respectively); these changes were associated to a similar increase in apo AI production rates (PR) (1.24+/-0.62 and 1.14+/-0.40 versus 0.53+/-0.17 mg/kg/h, p < 0.01). Consequently, apo AI plasma levels in pioglitazone-treated animals were similar to those of controls. The apo AI-FRC and -PR correlated with the relative proportion of the HDL3c subclass, as determined by polyacrylamide gradient electrophoresis. Our data demonstrate that pioglitazone markedly modifies apo AI kinetics and enhances the proportion of small HDL3c particles, despite the unchanged apo AI concentration. Whether or not the pioglitazone-induced structural changes of HDL contribute to the anti-atherosclerotic effects of the drug remains to be determined.