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Methods and Protocols
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6 January 2026

Repeatability and Variability of a High-Fat High-Fructose Diet-Induced Metabolic Syndrome Model in Young Adult Male Wistar Rats

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1
Department of Biochemistry, Medical University of Varna, 55 Marin Drinov Str., 9002 Varna, Bulgaria
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Department of Pharmacology and Clinical Pharmacology and Therapy, Medical University of Varna, 55 Marin Drinov Str., 9002 Varna, Bulgaria
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Department of General and Clinical Pathology, Medical University of Varna, 55 Marin Drinov Str., 9002 Varna, Bulgaria
*
Author to whom correspondence should be addressed.
This article belongs to the Section Biomedical Sciences and Physiology

Abstract

Metabolic syndrome is a disorder of energy metabolism characterized by persistently high prevalence and significant medical and economic burden on society. An effective animal model that closely replicates the key features of the syndrome in humans is essential for evaluating therapeutic strategies aimed at improving health outcomes. High-calorie diet-induced animal models of metabolic syndrome are preferred by many research groups for studying its pathogenesis, prevention and therapy. However, there are numerous variations in the types and proportions of carbohydrates and/or fats in the diets used. In 2015, our research team developed a diet-induced model of metabolic syndrome in young adult male Wistar rats that was based on adding 17% animal fat and 17% fructose to the standard rat chow and 10% fructose to the drinking water. This model reliably induced the morphometric and biochemical alterations that represent the core diagnostic features of the syndrome in humans. Since its initial introduction, we have utilized the high-fat high-fructose diet-induced model of metabolic syndrome/obesity in ten experimental studies. The current paper provides a protocol for applying the model, presents its repeatability and discusses the variability in the morphometric, biochemical, histopathological, immunohistochemical, and behavioral data of 10 experimental studies on Wistar rats.

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