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However, gaps remain in our understanding of the molecular mechanisms underlying these benefits and how to optimize exercise prescriptions for cardiometabolic disease. Animal models are indispensable tools for unraveling these mechanisms and translating findings to human health for improved management of these conditions. Rodent exercise models (eg, treadmill running and wheel running) dominate preclinical research, while resistance training models and high-intensity interval training models have gained in popularity in recent years. This review provides a comprehensive evaluation of existing animal models for cardiometabolic disease and exercise, highlighting their strengths, limitations, and translational relevance. We emphasize the critical need for research to support our mechanistic understanding of the multiorgan health benefits for the prevention of cardiometabolic diseases. In addition, we also highlight the need for research applying well-defined exercise interventions with preclinical disease models to provide translational data to guide future clinical applications for patients with cardiometabolic diseases.<\/jats:p>","DOI":"10.1161\/circresaha.124.325704","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T18:00:17Z","timestamp":1751565617000},"page":"139-162","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Animal Models of Exercise and Cardiometabolic Disease"],"prefix":"10.1161","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1438-8467","authenticated-orcid":true,"given":"Gengfu","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Applied Physiology and Kinesiology (G.D., T.E.R.), University of Florida, Gainesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-029X","authenticated-orcid":true,"given":"Terence E.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology (G.D., T.E.R.), University of Florida, Gainesville."},{"name":"Center for Exercise Science (T.E.R.), University of Florida, Gainesville."},{"name":"Myology Institute (T.E.R., K.A.E.), University of Florida, Gainesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5791-1441","authenticated-orcid":true,"given":"Karyn A.","family":"Esser","sequence":"additional","affiliation":[{"name":"Department of Physiology and Aging (K.A.E.), University of Florida, Gainesville."},{"name":"Myology Institute (T.E.R., K.A.E.), University of Florida, Gainesville."},{"name":"Claude D. 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