Lipasin is a recently identified lipokine expressed predominantly in liver and in adipose tissue. It was linked to insulin resistance in mice and to type 1 and type 2 diabetes (T1D, T2D) in humans. No metabolic studies concerning lipasin were performed yet in rats. Therefore, we used rat model of T2D and insulin resistance, Goto-Kakizaki (GK) rats, to determine changes of lipasin expression in liver and in white adipose tissue (WAT) over 52 weeks in the relation to glucose tolerance, peripheral tissue insulin sensitivity and adiposity. GK rats were grossly glucose intolerant since the age of 6 weeks and developed peripheral insulin resistance at the age of 20 weeks. Expression of lipasin in the liver did not differ between GK and Wistar rats, declining with age, and it was not related to hepatic triacylglycerol content. In WAT, the lipasin expression was significantly higher in Wistar rats where it correlated positively with adiposity. No such correlation was found in GK rats. In conclusion, lipasin expression was associated neither with a mild age-related insulin resistance (Wistar), nor with severe genetically-based insulin resistance (GK)., M. Cahová, D. Habart, T. Olejár, Z. Berková, Z. Papáčková, H. Daňková, A. Lodererova, M. Heczková, F. Saudek., and Obsahuje bibliografii
Prague hereditary hypercholesterolemic (PHHC) rat – rat strain crossbred from Wistar rats – is a model of hypercholesterolemia induced by dietary cholesterol. Importantly, no bile salts and/or antithyroid drugs need to be added to the diet together with cholesterol to induce hypercholesterolemia. PHHC rats have only modestly increased cholesterolemia when fed a standard chow and develop hypercholesterolem ia exceeding 5 mmol/l on 2 % cholesterol diet. Most of the cholesterol in hypercholesterolemic PHHC rats is found in VLDL that become enriched with cholesterol (VLDL-C/VLDL-TG ratio > 1.0). Concurrently, both IDL and LDL concentrations rise without any increase in HDL. PHHC rats do not markedly differ from Wistar rats in the activities of enzymes involved in intravascular remodelation of lipoproteins (lipoprotein and hepatic lipases and lecithin:cholesterol acyltransferase), LDL catabolism, cholesterol turnover rate and absorption of dietary cholesterol. The feeding rats with cholesterol diet results in development of fatty liver in spite of suppression of cholesterol synthesis. However, even though cholesterolemia in PHHC rats is comparable to human hypercholesterolemia, the PHHC rats do not develop atherosclerosis even after 6 months on 2 % cholesterol diet. Importantly, the crossbreeding experiments documented that hypercholesterolemia of PHHC rats is polygenic. To identify the genes that may be involved in pathogenesis of hypercholesterolemia in this strain, the studies of microarray gene expression in the liver of PHHC rats are currently in progress., J. Kovář ... [et al.]., and Obsahuje seznam literatury
The Prague Hereditary Hypercholesterolemic (PHHC) rat is a model of hypercholesterolemia. In previous experiments, it was found to be completely resistant to the development of atherosclerosis. It was assumed that the reverse transport of cholesterol (RCT) might be the reason for this resistance. In this study, RCT was measured in vivo by cholesterol efflux from macrophages to plasma, using previously established methods for RCT in mice (Rader 2003), optimized for measurements in rats. Primary cell culture of macrophages was labeled with 14Ccholesterol and then injected intraperitoneally into rats. Plasma and feces were collected at 24 and 48 h. The plasma 14Ccholesterol levels at both 24 and 48 h were significantly higher in male PHHC rats compared to control Wistar rats. The PHHC rats excreted less 14C-cholesterol in feces in 24 and 48 h compared to Wistar rats. The largest pool of 14C-cholesterol was found in the adipose tissue of PHHC rats and in contrast lower levels of 14Ccholesterol were measured in the liver and muscle tissues of PHHC rats compared with Wistar rats. Increasing release of 14Ccholesterol efflux from macrophages demonstrates accelerated RTC and leads to prevention of atherogenesis in PHHC rats., M. Schmiedtova, M. Heczkova, J. Kovar, I. Kralova Lesna, R. Poledne., and Obsahuje bibliografii
To understand the pathogenesis of hypercholesterolemia in Prague hereditary hypercholesterolemic (PHHC) rat, we analyzed the response of hepatic transcriptome to dietary cholesterol in PHHC and control Wistar rats. Male PHHC and Wistar rats were fed chow (C), 5 % fat (palm kernel oil) (CF) or 1 % cholesterol + 5 % fat (CHOL) diet for three weeks. Hepatic transcriptome was analyzed using Affymetrix GeneChip arrays. No differences were found in the effect of both control diets (C and CF) on lipid metabolism and gene expression of 6500 genes. Therefore, these data were pooled for further analysis. Dietary cholesterol induced accumulation of cholesterol and triacylglycerols in the liver in both strains and hypercholesterolemia in PHHC rats. However, there were no differences in response of hepatic transcriptome to CHOL diet. On the other hand, several genes were found to be differently expressed between both strains independently of the diet. Two of those genes, Apof and Aldh1a7, were studied in more detail, and their role in pathogenesis of hypercholesterolemia in PHHC rats could not been corroborated. In conclusion, the hypercholesterolemia in PHHC rats is due to physiological response of hepatic transcriptome to dietary cholesterol in different genetic background., M. Vlachová, M. Heczková, M. Jirsa, R. Poledne, J. Kovář., and Obsahuje bibliografii