Exercise improves cardiorespiratory fitness and quality of life in heart failure with preserved ejection fraction (HFpEF), but its effects on cardiac remodelling and the impact of different exercise modalities remain unclear. This study investigated how distinct exercise regimens influence cardiac function and molecular signatures in a murine cardiometabolic HFpEF model, focusing on modality-specific transcriptional changes. Six-week-old male C57BL6 mice were fed control chow or a 60% high-fat diet plus L-NAME for 14 weeks. After 7 sedentary weeks, mice were randomised to remain sedentary or undergo hybrid treadmill or voluntary wheel-running exercise for 7 weeks. Single-hit groups (HFD or L-NAME alone) were included for comparison. Cardiac phenotyping, exercise testing, and left ventricular bulk RNA sequencing were performed with differential expression and pathway analyses. Sedentary HFpEF mice developed diastolic dysfunction (increased E/e’, prolonged IVRT, reduced GLS). Hybrid exercise improved diastolic function and exercise capacity, whereas voluntary aerobic exercise did not, despite unchanged body weight. Transcriptomic profiling revealed distinct cardiac responses to diet and exercise. Hybrid exercise upregulated mitochondrial oxidative phosphorylation genes and attenuated HFpEF-associated circadian dysregulation, changes not observed with aerobic exercise. These molecular adaptations aligned with improved cardiac function. Overall, structured hybrid exercise exerted superior effects on function and induced distinct metabolic and circadian transcriptional remodelling, highlighting exercise modality as a key determinant of benefit in cardiometabolic HFpEF.
Celebrating Physiology in Cambridge (University of Cambridge, UK) (2026) Proc Physiol Soc 76, SA02
Research Symposium: Structured hybrid exercise restores cardiac function in murine cardiometabolic HFpEF
Satoshi Bujo1, Ankur Saini1, Guillame Bidault2, Murray Clarke 3, Thomas Krieg4, Antonio Vidal Puig5, Ana Vujic6
1Department of Medicine, Victor Phillip Dahdaleh Heart and Lung Research Institute,University of Cambridge, Cambridge, UK, UK, 2Institute of Metabolic Science, University of Cambridge, Cambridge, UK UK, 3Department of Me
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.