Оценка влияния агониста рецепторов инкретинов на показатели липидного и углеводного обмена при экспериментальной хронической гиперлипидемии у крыс: БИОХИМИЯ

Николай Сергоевич  Деданишвили; Сарнг Саналович  Пюрвеев; Екатерина Геннадьевна  Батоцыренова; Вадим Анатольевич  Кашуро; Андрей Глебович  Васильев

Evaluation of the influence of an incretinous receptor agonist on lipid and carbohydrate metabolism indicators in experimental chronic hyperlipidemia in rats

BIOCHEMISTRY

Nikolay S. Dedanishvili Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0001-6231-445X
Sarng S. Pyurveev Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0002-4467-2269
Ekaterina G. Batotsyrenova Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0003-3827-4579
Vadim A. Kashuro Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0002-7892-0048
Andrey G. Vasiliev Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0002-7493-7619

Keywords:

chronic hyperlipidemia high fat high cholesterol diet tirzepatide GLP-1 GIP total cholesterol triacylglycerols glucose хроническая гиперлипидемия высокожировая высокохолестериновая диета тирзепатид GLP-1 GIP общий холестерин триацилглицериды глюкоза

Abstract

Introduction. Lipid metabolism disorders are key factors in the development of atherosclerosis, metabolic syndrome, and type 2 diabetes. Incretin-based drugs, which possess not only antihyperglycemic but also pronounced metabolic effects, have attracted particular interest in recent years. Tirzepatide, a dual GIP and GLP-1 receptor agonist, has demonstrated the ability to improve lipid and carbohydrate metabolism in clinical studies; however, its effects in experimental chronic hyperlipidemia have not been adequately studied. Aim of the study: to evaluate the effects of tirzepatide on lipid and carbohydrate metabolism in rats with experimental chronic hyperlipidemia induced by a high-fat, high-cholesterol diet. Materials and methods. The study was performed on mature male Wistar rats (n=24). Chronic hyperlipidemia was modeled by administering a high-fat, high-cholesterol diet for 4 weeks. Animals were divided into five groups: intact control, a hypercholesterol diet, and a hypercholesterol diet combined with tirzepatide. Tirzepatide was administered subcutaneously at a dose of 0.30 mg/kg once daily during the final 7 days of the experiment while the animals continued to consume the high-cholesterol diet. Serum total cholesterol, triacylglycerols, and glucose concentrations were determined using an enzymatic colorimetric method. Statistical data processing was performed using Graph Pad Prism 10.0. Differences were considered statistically significant at p <0.05. Results. In animals fed a high-fat, high-cholesterol diet, the development of pronounced metabolic disorders was revealed, manifested by an increase in the concentration of total cholesterol by 3.7 times (3.741±0.382 versus 0.999±0.123 mmol/l; p <0.0001), triacylglycerols by 2.8 times (2.275±0.115 versus 0.804±0.096 mmol/l; p <0.0001) and glucose by 38.7% (7.20±0.24 versus 5.19±0.47 mmol/l; p=0.0019) compared to the intact control. Administration of tirzepatide resulted in a significant reduction in total cholesterol to 2.548±0.141 mmol/L (–31.9%; p=0.0109), triacylglycerols to 1.174±0.069 mmol/L (–48.4%; p <0.0001), and glucose to 5.653±0.096 mmol/L (–21.4%; p <0.0001) relative to animals on the hypercholesterol diet. The most pronounced effect of tirzepatide was observed in reducing triacylglycerol levels. Conclusions. Four weeks of high-fat, high-cholesterol diet resulted in experimental chronic hyperlipidemia, accompanied by lipid and carbohydrate metabolism disorders. Seven-day administration of tirzepatide during continued consumption of a high-fat, high-cholesterol diet significantly improved metabolic parameters, reducing serum concentrations of total cholesterol, triacylglycerols, and glucose. These data support the potential of dual GIP/GLP-1 receptor agonists for the correction of metabolic disorders associated with chronic hyperlipidemia.

Author Biographies

Nikolay S. Dedanishvili, Saint Petersburg State Pediatric Medical University

Postgraduate Student, Dept. of Biological Chemistry

Sarng S. Pyurveev, Saint Petersburg State Pediatric Medical University

Cand. Sci. (Med.), Associate Professor, Dept. of Pathological Physiology with a course in Immunopathology

Ekaterina G. Batotsyrenova, Saint Petersburg State Pediatric Medical University

Dr. Sci. (Biol.), Associate Professor, Head, Dept. of General and Medicinal Chemistry named after prof. V.V. Khorunzhy; Professor, Dept. of Biological Chemistry

Vadim A. Kashuro, Saint Petersburg State Pediatric Medical University

Dr. Sci. (Med.), Associate Professor, Head, Dept. of Biological Chemistry

Andrey G. Vasiliev, Saint Petersburg State Pediatric Medical University

Dr. Sci. (Med.), Professor, Head, Dept. of Pathological Physiology with a Course in Immunopathology

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