Animal models of obesity and diabetes mellitus for dietary bioactive component development: A systematic review
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GRAPHICAL ABSTRACT
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PUBLIC SUMMARY
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Diet-induced rodent models dominate bioactive research.
Outcome reporting is skewed toward basic metabolic markers.
Mechanistic depth varies and is often limited.
Sex bias and design variability affect reproducibility.
A framework is proposed to guide animal model selection.
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ABSTRACT
Animal models are widely used to investigate the metabolic effects of dietary bioactive compounds in obesity and type 2 diabetes mellitus (T2DM). However, unlike conventional drugs, dietary bioactives often exert pleiotropic and context-dependent effects that are strongly influenced by disease severity, dietary background, and experimental conditions. Consequently, model selection and methodological variability may affect the reproducibility and translational relevance of preclinical findings. This systematic review evaluated animal models used in dietary bioactive research, identified methodological trends and limitations, and proposed a framework to guide future model selection. A systematic search of PubMed, Scopus, Web of Science, ScienceDirect, SpringerLink, and Wiley Online Library was conducted for studies published within the last five years. Data were extracted on species, strain, model type, dietary induction, intervention characteristics, outcome measures, and mechanistic depth. A total of 194 studies were included. Diet-induced obesity models were the most frequently used (67.2%), followed by genetic, hybrid, and chemically induced models. Rodents, particularly mice and rats, predominated, while alternative models such as zebrafish and invertebrates were used infrequently. Outcome reporting focused mainly on body weight, glucose metabolism, and lipid profiles, whereas mechanistic investigations varied considerably. Substantial methodological heterogeneity was observed in diet composition, dosing strategies, study duration, and reporting quality, alongside a marked bias toward male animals. Overall, current preclinical research is characterized by model dominance, methodological variability, and inconsistent mechanistic validation. The proposed framework provides a structured approach to improve study design and enhance the translational relevance of dietary bioactive research in metabolic disease.-
Keywords:
- Animal models /
- Dietary bioactives /
- Obesity /
- Type 2 diabetes /
- Metabolic syndrome /
- Model selection.
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REFERENCES
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Cite this article:
Randeni N., Luo J. and Xu B. (2026). Animal models of obesity and diabetes mellitus for dietary bioactive component development: A systematic review. The Innovation Nutrition 1:100029. https://doi.org/10.59717/j.xinn-nutri.2026.100029
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Randeni N., Luo J. and Xu B. (2026). Animal models of obesity and diabetes mellitus for dietary bioactive component development: A systematic review. The Innovation Nutrition 1:100029. https://doi.org/10.59717/j.xinn-nutri.2026.100029
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Content
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Figure 1.
PRISMA flow diagram of the overall study process.
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Figure 2.
Distribution of animal models used in the included studies
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Figure 3.
Distribution of animal models used in the included studies
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Figure 4.
Distribution of dietary bioactive compounds investigated in the included studies
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Figure 5.
Outcome reporting patterns and mechanistic depth across studies
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Figure 6.
Framework for selection of animal models in dietary bioactive research for metabolic disorders.
