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 Jose Justo da Silva; Mattia Scalabrin; Xinyue Yu; Ziyi Zhong; Michael A Colman; Nadira Y Yuldasheva; George W Booz; Volker Adams; Marcelo G Pereira; Alessandro Cataliotti; Lee D Roberts; Stuart Egginton; T Scott Bowen

doi:10.1016/j.jacbts.2023.09.014

Caloric Restriction Rejuvenates Skeletal Muscle Growth in Heart Failure With Preserved Ejection Fraction

JACC Basic Transl Sci. 2023 Dec 6;9(2):223-240. doi: 10.1016/j.jacbts.2023.09.014. eCollection 2024 Feb.

Authors

Ever Espino-Gonzalez¹, Peter G Tickle¹, Raffaele Altara^{2

3}, Harrison Gallagher¹, Chew W Cheng⁴, Viktor Engman¹, Nathanael Wood¹, Gustavo Jose Justo da Silva⁵, Mattia Scalabrin¹, Xinyue Yu¹, Ziyi Zhong¹, Michael A Colman¹, Nadira Y Yuldasheva⁴, George W Booz⁶, Volker Adams⁷, Marcelo G Pereira¹, Alessandro Cataliotti⁵, Lee D Roberts⁴, Stuart Egginton¹, T Scott Bowen¹

Affiliations

¹ School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
² Department of Anatomy & Embryology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands.
³ Department of Pathology, School of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
⁴ Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine, University of Leeds, Leeds, United Kingdom.
⁵ Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
⁶ Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
⁷ Heart Center Dresden, TU-Dresden, Dresden, Germany.

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.

Keywords: HFpEF; diet; exercise training; mitochondria; skeletal muscle.