Guidelines for diet-induced models of cardiometabolic syndrome
- 1 October 2025
- journal article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 329 (4) , H974-H988
Abstract
Cardiometabolic syndrome (CMS) encompasses a cluster of metabolic abnormalities, including obesity, insulin resistance, dyslipidemia, and hypertension, that collectively increase the risk of cardiovascular disease and type 2 diabetes. Animal models are widely used to study CMS, with diet-induced models being the most physiologically relevant. A lack of reporting standards and variability in dietary composition, feeding duration, and macronutrient content across studies hinder reproducibility assessment and translational impact evaluation. We provide standardized guidelines for the consideration, preparation, and use of diets in experimental models of CMS. Advantages and limitations of different diet-induced models are compared with genetic and pharmacological approaches, emphasizing replicability to human metabolic dysregulation. Key components include macronutrient composition, fat source selection, feeding duration, strain susceptibility, and sex differences. In addition, we outline husbandry practices, including environmental factors, bedding material, and enrichment conditions, which can affect metabolic outcomes. Standardization is essential for enhancing experimental reproducibility and facilitating cross-study comparisons. These guidelines serve as a framework for researchers to optimize dietary interventions in CMS models, improving the predictive value of preclinical findings for translational applications to aid in the development of targeted therapeutic strategies.Keywords
Funding Information
- HHS | National Institutes of Health (GM151274)
- HHS | National Institutes of Health (R01HL155618)
- U.S. Department of Veterans Affairs (I01CX002780)
- American Heart Association (25IVPHA1462290)
- Federal Government | DHAC | National Health and Medical Research Council (APP2029251)
- Department of Health, Disability and Ageing (MRF2023754)
- Takeda Science Foundation (2022060878)
- Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (PICT 2019-02987)
- Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 938)
- HHS | National Institutes of Health (UC2MD019626)
- HHS | National Institutes of Health (R21OD037867)
- Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (PICT 2018-03267)
This publication has 185 references indexed in Scilit:
- Targeting Rab7‐Rilp Mediated Microlipophagy Alleviates Lipid Toxicity in Diabetic CardiomyopathyAdvanced Science, 2024
- Modeling Diet‐Induced Metabolic Syndrome in RodentsMolecular Nutrition & Food Research, 2020
- Mouse Models of Autoimmune Diabetes: The Nonobese Diabetic (NOD) Mouse2020
- Endothelial Lipase Is an Alternative Pathway for Fatty Acid Release from Lipoproteins: Evidence from a High Fat Diet Model of Obesity in RatsLipids, 2018
- Cellular apoptosis and cardiac dysfunction in STZ‐induced diabetic rats attenuated by anthocyanins via activation of IGFI‐R/PI3K/Akt survival signalingEnvironmental Toxicology, 2017
- Earlier onset of diabesity‐Induced adverse cardiac remodeling in female compared to male miceObesity, 2015
- Housing experimental rats in solid‐based cages with digestible bedding may confound outcomes of nutritional studiesJournal of the Science of Food and Agriculture, 2014
- Variations in body weight, food intake and body composition after long-term high-fat diet feeding in C57BL/6J miceObesity, 2014
- The mechanisms of alloxan- and streptozotocin-induced diabetesDiabetologia, 2007
- Substitution at Codon 269 (Glutamine → Proline) of the Leptin Receptor (OB-R) cDNA Is the Only Mutation Found in the Zucker Fatty (fa/fa) RatBiochemical and Biophysical Research Communications, 1996