Caloric Restriction Rejuvenates Skeletal Muscle Growth in Heart Failure With Preserved Ejection Fraction
Ever Espino‐Gonzalez, Peter G. Tickle, Raffaele Altara, Harrison Gallagher, Chew W. Cheng, Viktor Engman, Nathanael Wood, Gustavo José Justo da Silva, Mattia Scalabrin, Xinyue Yu, Ziyi Zhong, Michael A. Colman, Nadira Yuldasheva, George W. Booz, Volker Adams, Marcelo G. Pereira, Alessandro Cataliotti, Lee D. Roberts, Stuart Egginton, T. Scott Bowen
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a major clinical problem, with limited treatments. HFpEF is characterized by a distinct, but poorly understood, skeletal muscle pathology, which could offer an alternative therapeutic target. In a rat model, we identified impaired myonuclear accretion as a mechanism for low myofiber growth in HFpEF following resistance exercise. Acute caloric restriction rescued skeletal muscle pathology in HFpEF, whereas cardiac therapies had no effect. Mechanisms regulating myonuclear accretion were dysregulated in patients with HFpEF. Overall, these findings may have widespread implications in HFpEF, indicating combined dietary with exercise interventions as a beneficial approach to overcome skeletal muscle pathology.