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Comparative characteristics of in vivo models of hyperlipidemia in Wistar rats and C57Bl/6 mice

Abstract

In vivo simulation of lipid disorders (hyperlipidemia, obesity, metabolic syndrome, atherosclerosis) is of considerable interest to search for genomic, transcriptomic and metabolomic markers that allow for differential diagnosis, prognosis and selection of personalized diet therapy in patients with such pathology. The aim of the study was the development and characterization of basic biochemical parameters of in vivo models of alimentary hyperlipidemia in outbred rats and inbred mice. The experiment was con­ducted on 48 growing female Wistar rats, and 48 growing female mice of line C57Black/6, which were divided into 12 groups of 8 animals per group. Within 63 days the rats and mice of first (control) group received a balanced semi synthetic diet (BD), the animals of the second groups - high-fat diet (HFD) with 30% of the total fat by weight of dry feed, third groups - BD and fructose solution (Fr) instead of water, the fourth groups -HFD + Fr, fifth groups - BD supplemented with 0.5% cholesterol (Cho) by weight of dry feed, sixth groups - BD with Cho and Fr. The amount and composition of diets consumed were corrected during the experiment for their closest approach in calories. After removal of animals from the experiment there were determined the mass of internal organs, HDL, LDL, total cholesterol, triglycerides, glucose in blood plasma, total lipids and their fatty acid composition in liver, ghrelin, GIP, GLP-1, glucagon, leptin, PAI-1, resistin levels in blood plasma. It was found that in both species the liver is the most sensitive to nutritional imbalance, nutrient exerting the greatest impact on this was Fr. In rats, as compared to mice, there was significantly more pronounced shifts in lipoprotein spectrum in response to nutritional imbalances, especially to the consumption of additional Cho, which was manifested in an increase of LDL, decrease of HDL and magnification of atherogenic index. In the liver of rats fed diets with Cho, marked steatosis developed manifested in a disproportionate increase in the lipid content and accompanied by changes in their fatty acid composition, especially in the ratio ω6 to ω3 PUFAs. Changing of hormones - regula­tors of carbohydrate metabolism (GLP, glucagon) and ghrelin was significantly greater in mice than in rats as a result of consumption of additional Fr. Effect had the opposite direction in two species of Cho and Fr combining on leptin levels. The significance is dis­cussed of the revealed interspecies differences in the light of the characteristics of lipid and glucose metabolism in these two lines of animals that are the most common models of alimentary-dependent diseases.

Keywords:hyperlipidemia, in vivo model, rats, mice, cholesterol, fructose, peptide hormones


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