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

Area of Science:

• Cardiology
• Exercise Physiology
• Skeletal Muscle Biology

Background:

• Heart failure with preserved ejection fraction (HFpEF) presents significant clinical challenges with few effective treatments.
• A poorly understood skeletal muscle pathology is a hallmark of HFpEF, suggesting it as a potential therapeutic target.

Purpose of the Study:

• To investigate the skeletal muscle pathology in HFpEF and identify mechanisms underlying impaired myofiber growth.
• To evaluate the efficacy of caloric restriction and cardiac therapies in ameliorating HFpEF-related skeletal muscle dysfunction.

Main Methods:

• Utilized a rat model of HFpEF to study myofiber growth following resistance exercise.
• Assessed the impact of acute caloric restriction and cardiac therapies on skeletal muscle pathology.
• Examined the regulation of myonuclear accretion in HFpEF patients.

Main Results:

• Identified impaired myonuclear accretion as a key mechanism limiting myofiber growth in HFpEF after resistance exercise.
• Acute caloric restriction effectively rescued skeletal muscle pathology in the HFpEF rat model.
• Cardiac therapies demonstrated no beneficial effect on skeletal muscle pathology.
• Dysregulation of myonuclear accretion mechanisms was observed in HFpEF patients.

Conclusions:

• Impaired myonuclear accretion contributes to skeletal muscle pathology in HFpEF.
• Dietary interventions, specifically caloric restriction, show promise in treating HFpEF-related skeletal muscle issues.
• Combined dietary and exercise interventions may offer a beneficial strategy for managing HFpEF by targeting skeletal muscle dysfunction.