Effects of the Hyperlipidemic Diet on the Rat Blood Metabolome: Pilot Study Results

Abstract

Introduction: Imbalanced nutrition and the predominance of lipid and carbohydrate components in it leads to vascular damage and, as a consequence, cardiovascular diseases, which are the leading cause of death worldwide. Metabolomic screening can predict the presence of the disease in the early stages and help in tracking the effectiveness of treatment. Objective: To conduct a pilot study by in vivo modeling of hyperlipidemia and hypercholesterolemia to investigate metabolomic alterations in the blood plasma of rats and to search for new biomarkers of atherosclerotic vascular lesions. Materials and methods: The study involved 30 albino male rats divided into two groups: the experimental group (n = 15) and the control group (n = 15). Modeling of atherosclerosis was carried out by means of a diet with an excess of simple sugars, fat and cholesterol, coupled with pharmacological effects, which consisted of inducing hypothyroidism in combination with a toxic dose of vitamin D. Blood metabolomic profiling was performed using liquid chromatography – tandem mass spectrometry. Results: Our experiment with the comprehensive in vivo modeling of hyperlipidemia in the experimental group showed a decrease by 1.3 to 1.8 times in the levels of various acylcarnitines, by 1.4 and 2 times of some indole derivatives, and by 3.5 and 3.9 times of some fatty acids. At the same time, an increase was observed for ophthalmate by 1.8 times, sterol by 2.2 times, and glycocholic acid by 5.6 times, whereas 1.2 to 1.9-fold multidirectional changes were established for glycerophospholipids. Conclusions: The experiment has provided data related to various aspects of the disease, such as hyperlipidemia, inflammation, oxidative stress, blood rheology, and body weight of the animals. Metabolomic profiling, in its turn, helped established potential molecular biomarkers of the pathological processes.