Rats of hypertensive ISIAH strain are resistant to the development of metabolic syndrome induced by high-fat diet.

We studied the influence of high-fat diet on the development of metabolic syndrome in rats of hypertensive ISIAH strain and normotensive WAG strain. In contrast to ISIAH rats, high-fat diet in WAG rats led visceral obesity, glucose tolerance, and dyslipidemia. DNA-binding activity of the peroxisome proliferator-activated receptor α (PPARα) decreased in the liver of WAG rats and increased in ISIAH rats. Blood levels of TNF-α, IL-6, and corticosterone increased more significantly in WAG rats. Corticosterone content in the adrenal glands was more markedly reduced in WAG rats. High-fat diet had no effect on BP in ISIAH and WAG rats. It was concluded that ISIAH rats can be used as a genetic model in studies of the mechanism of resistance to the metabolic syndrome.

Lipid synthesis in macrophages during inflammation in vivo: effect of agonists of peroxisome proliferator activated receptors alpha and gamma and of retinoid X receptors.

The effects of peroxisome proliferator activated receptors alpha and gamma (PPAR-alpha and PPAR-gamma) and retinoid X receptor (RXR) agonists upon synthesis and accumulation of lipids in murine C57Bl macrophages during inflammation induced by injection of zymosan and Escherichia coli lipopolysaccharide (LPS) have been studied. It is significant that intraperitoneal injection of zymosan (50 mg/kg) or LPS (0.1 mg/kg) in mice led to a dramatic increase of [14C]oleate incorporation into cholesteryl esters and triglycerides and [14C]acetate incorporation into cholesterol and fatty acids in peritoneal macrophages. Lipid synthesis reached its maximum rate 18-24 h after injection and was decreased 5-7 days later to control level after LPS injection or was still heightened after zymosan injection. In macrophages obtained in acute phase of inflammation (24 h), degradation of 125I-labeled native low density lipoprotein (NLDL) was 4-fold increased and degradation of 125I-labeled acetylated LDL (AcLDL) was 2-3-fold decreased. Addition of NLDL (50 microg/ml) or AcLDL (25 microg/ml) into the incubation medium of activated macrophages induced 9-14- and 1.25-fold increase of cholesteryl ester synthesis, respectively, compared with control. Addition of NLDL and AcLDL into the incubation medium completely inhibited cholesterol synthesis in control macrophages but had only slightly effect on cholesterol synthesis in activated macrophages. Injection of RXR, PPAR-alpha, or PPAR-gamma agonists--9-cis-retinoic acid (5 mg/kg), bezafibrate (10 mg/kg), or rosiglitazone (10 mg/kg), respectively--30 min before zymosan or LPS injection led to significant decrease of lipid synthesis. Ten hour preincubation of activated in vivo macrophages with the abovementioned agonists (5 microM) decreased cholesteryl ester synthesis induced by NLDL and AcLDL addition into the cell cultivation medium. The data suggest that RXR, PPAR-alpha, or PPAR-gamma agonists inhibited lipid synthesis and induction of cholesteryl ester synthesis in inflammatory macrophages caused by capture of native or modified LDL.

Binding and transport of benzo[a]pyrene by blood plasma lipoproteins: the possible role of apolipoprotein B in this process.

The role of plasma lipoproteins as carriers in the transport of benzo[a]pyrene was assessed in in vitro and in vivo studies. Addition of [3H]benzo[a]pyrene to rat plasma resulted in binding of the xenobiotic to lipoproteins. Studies of labeled benzo[a]pyrene distribution in rat blood plasma by the method of ultracentrifugation have given the following results: high-density lipoproteins, 40%; low-density lipoproteins, 14%; very-low-density lipoproteins, 23%; other plasma proteins, 23%. Complexes of benzo[a]pyrene-lipoproteins were isolated by gel filtration with Sephadex G-25 and used for intravenous injection in rats. Biodistribution studies have shown different localization of benzo[a]pyrene in rat organs and tissues depending on lipoprotein classes. A high amount or radioactivity was bound by the liver and adrenals when all classes of lipoproteins were used, but especially with high-density lipoproteins. High levels of benzo[a]pyrene were measured in the kidneys. Equilibrium dissociation constants for complexes of benzo[a]pyrene with high-density lipoproteins and low-density lipoproteins were obtained (Kd 4.1 x 10(-5) and 1.5 x 10(-5) M, respectively). Binding and distribution of the protein component of lipoproteins were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. More than 80% of the radioactivity recovered from the gel was localized in the area of apolipoprotein B. After isolation and purification of apolipoprotein B, the equilibrium dissociation constant for complexes of benzo[a]pyrene with apolipoprotein B was obtained, and its value indicated that apolipoprotein B might be the main protein carrier for benzo[a]pyrene.

[Evaluation of the binding of benzo-a-pyrene by blood serum lipoproteins using the cellulose disk method]. / Otsenka sviazyvaniia benzo-a-pirena lipoproteinami syvorotki krovi metodom bumazhnykh diskov.

A simple and convenient method has been developed for evaluation binding capacity of lipophilic ligands with lipoproteins or other transport proteins. For this purpose cellulose discs (Whatman 3 MM) were loaded with the constant quantity of 3H-benzopyrene and increasing amounts of unlabelled benzo[a]pyrene in dimethylsulfoxide, dried up and incubated in solution of lipoproteins. Dissociation constants were deduced from the remained disk radioactivity using the Scatchard plot method. The obtained values of the dissociation constants were: HDL--4.1 x 10(-5) M; LDL--1.5 x 10(-6) M; VLDL--8.8 x 10(-6) M.

[Characteristics of binding and transport of benzo(a)pyrene by blood serum lipoproteins]. / Kharakteristika sviazyvaniia i transporta benz(a)pirena s lipoproteidami syvorotki krovi.

Binding and distribution of 3H-benzo[a]pyrene in lipoprotein fraction of rat blood serum were studied. The binding was enhanced in the row: LDL, VLDL, HDL, Kd lipoprotein-benzo[a]pyrene complexes had been calculated by means of tryptophan fluorescence quenching. It was found, that Kd value benzo[a]pyrene complexes with VLD was 1.5 x 10(-6) M, with LDL -6.6 x 10(-7) M and with HDL -4.2 x 10(-6) M. Radiolabeled benzo[a]pyrene uptake by rat organs and tissues was investigated after i.v. injection of benzo[a]pyrene-complexes with LP of different classes. High uptake activity was revealed for liver, adrenals and kidneys, whereas heart, spleen, thymus were characterized by low 3H-benzo[a]pyrene accumulation. Radioactivity distribution pattern was depended on the class of LP used for complexation. Ours data permit to evaluate the participation of lipoproteins in transport and metabolic pathways of xenobiotics in organism.