Exercise Therapy Rescues Skeletal Muscle Dysfunction and Exercise Intolerance in Cardiometabolic HFpEF
Heather Quiriarte, Robert C. Noland, James Stampley, Gregory K. Davis, Zhen Li, Eunhan Cho, Youyoung Kim, Jake E. Doiron, Guillaume Spielmann, Sujoy Ghosh, Sanjiv J. Shah, Brian A. Irving, David J. Lefer, Timothy D. Allerton
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.