Moderate-intensity interval exercise exacerbates cardiac lipotoxicity in high-fat, high-calories diet-fed mice

Jing Geng, Xiaoliang Zhang, Yanjie Guo, He Wen, Dong Guo, Qi Liang, Siying Pu, Ying Wang, Mingchuan Liu, Zhelong Li, Wei Hu, Xue Yang, Pan Chang, Lang Hu () and Yan Li ()
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Jing Geng: Airforce Medical University
Xiaoliang Zhang: Airforce Medical University
Yanjie Guo: Xi’an International Medical Center Hospital
He Wen: Airforce Medical University
Dong Guo: Airforce Medical University
Qi Liang: Airforce Medical University
Siying Pu: Airforce Medical University
Ying Wang: Airforce Medical University
Mingchuan Liu: Airforce Medical University
Zhelong Li: Airforce Medical University
Wei Hu: Airforce Medical University
Xue Yang: Airforce Medical University
Pan Chang: The Second Affiliated Hospital of Xi’an Medical College
Lang Hu: Airforce Medical University
Yan Li: Airforce Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Physical exercise is a cornerstone for preventing diet-induced obesity, while it is unclear whether physical exercise could offset high-fat, high-calories diet (HFCD)-induced cardiac dysfunction. Here, mice were fed with HFCD and simultaneously subjected to physical exercise. As expected, physical exercise prevented HFCD-induced whole-body fat deposition. However, physical exercise exacerbated HFCD-induced cardiac damage. Further metabolomic analysis results showed that physical exercise induced circulating lipid redistribution, leading to excessive cardiac lipid uptake and lipotoxicity. Our study provides valuable insights into the cardiac effects of exercise in mice fed with HFCD, suggesting that counteracting the negative effect of HFCD by simultaneous physical exercise might be detrimental. Moreover, inappropriate physical exercise may damage certain organs even though it leads to weight loss and overall metabolic benefits. Of note, the current findings are based on animal experiments, the generalizability of these findings beyond this specific diet and mouse strain remains to be further explored.

Date: 2025
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DOI: 10.1038/s41467-025-55917-8

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