Exercise Therapy Rescues Skeletal Muscle Dysfunction and Exercise Intolerance in Cardiometabolic HFpEF

Area of Science:

• Cardiology
• Metabolic research
• Exercise physiology

Background:

• Exercise intolerance is a primary limitation in heart failure with preserved ejection fraction (HFpEF), particularly when obesity is present.
• The underlying mechanisms linking skeletal muscle metabolism to exercise intolerance in HFpEF remain incompletely understood.

Purpose of the Study:

• To investigate the efficacy of exercise therapy in reversing skeletal muscle dysfunction and exercise intolerance in a "2-hit" model of HFpEF.
• To elucidate the impact of exercise on skeletal muscle metabolism in the context of HFpEF and obesity.

Main Methods:

• Utilized a "2-hit" mouse model simulating HFpEF with obesity.
• Implemented voluntary wheel running as the exercise intervention.
• Employed advanced metabolic cages and a multiomic approach to assess skeletal muscle function and metabolism.

Main Results:

• Exercise therapy successfully restored impaired skeletal muscle lipid oxidation in mice with HFpEF.
• Exercise normalized branched-chain amino acid oxidation pathways in skeletal muscle.
• Restored metabolic function correlated with improved exercise capacity and reversal of exercise intolerance.

Conclusions:

• Exercise therapy can effectively reverse skeletal muscle metabolic dysfunction in HFpEF.
• Skeletal muscle metabolism plays a critical role in exercise intolerance associated with HFpEF.
• Targeting skeletal muscle metabolism through exercise represents a promising therapeutic strategy for HFpEF.