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

**Authors:** Danail Pavlov, Silvia Gancheva, Klementina Moneva-Marinova, Antoaneta Georgieva, Milena Todorova, Nadezhda Stefanova, Mehmed Reyzov, Elis Rafailova, Miroslav Eftimov, Maria Tzaneva, Stefka Valcheva-Kuzmanova, Maria Zhelyazkova-Savova

PMC · DOI: 10.3390/mps9010007 · Methods and Protocols · 2026-01-06

## TL;DR

This paper describes a reliable high-fat high-fructose diet model for metabolic syndrome in rats and evaluates its consistency and variability across multiple studies.

## Contribution

The study provides a detailed protocol and analysis of a repeatable metabolic syndrome model in Wistar rats.

## Key findings

- The high-fat high-fructose diet reliably induces metabolic syndrome features in young adult male Wistar rats.
- The model shows consistent morphometric and biochemical changes across ten experimental studies.
- Variability in histopathological and behavioral data was observed but remains within acceptable experimental ranges.

## 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.

## Linked entities

- **Chemicals:** fructose (PubChem CID 5984)
- **Diseases:** metabolic syndrome (MONDO:0000816), obesity (MONDO:0011122)

## Full-text entities

- **Diseases:** obesity (MESH:D009765), Metabolic Syndrome (MESH:D024821), disorder of energy metabolism (MESH:D008659)
- **Chemicals:** High-Fructose Diet (-), fructose (MESH:D005632), Fat (MESH:D005223), carbohydrates (MESH:D002241)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

137 references — full list in the complete paper: https://tomesphere.com/paper/PMC12821558/full.md

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Source: https://tomesphere.com/paper/PMC12821558