Abstract
Exercise intolerance, a hallmark of heart failure with preserved ejection fraction (HFpEF) exacerbated by obesity, involves unclear mechanisms related to skeletal muscle metabolism. In a “2-hit” model of HFpEF, we investigated the ability of exercise therapy (voluntary wheel running) to reverse skeletal muscle dysfunction and exercise intolerance. Using state-of-the-art metabolic cages and a multiomic approach, we demonstrate exercise can rescue dysfunctional skeletal muscle lipid and branched-chain amino acid oxidation and restore exercise capacity in mice with cardiometabolic HFpEF. These results underscore the importance of skeletal muscle metabolism to improve exercise intolerance in HFpEF.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1409-1425 |
| Number of pages | 17 |
| Journal | JACC: Basic to Translational Science |
| Volume | 9 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2024 |
Funding
The authors thank Dr Jarek Staszkiewicz for assistance with bioinformatic analysis. They would like to thank Dr Bernard Rees for the use of additional Oroboros O2ks, which were partly funded by the Louisiana Board of Regents (106ENH-22). The authors thank Dr Jarek Staszkiewicz for assistance with bioinformatic analysis. They would like to thank Dr Bernard Rees for the use of additional Oroboros O2ks, which were partly funded by the Louisiana Board of Regents (106ENH-22). The authors thank the IDeA National Resource for Quantitative Proteomics for their support of the Kinter Lab (R24GM137786).
Keywords
- branched-chained amino acids
- exercise
- heart failure with preserved ejection fraction
- metabolism
- mitochondria
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
