Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model

Area of Science:

• Cardiology
• Metabolic Diseases
• Skeletal Muscle Physiology

Background:

• Heart failure with preserved ejection fraction (HFpEF) involves peripheral skeletal muscle (SKM) dysfunction, leading to exercise intolerance.
• Sodium-Glucose-Transporter 2 inhibitors (SGLT2i) have shown promise in reducing cardiovascular events in HFpEF patients.

Purpose of the Study:

• To investigate the effects of Empagliflozin (Empa) on SKM function, metabolism, and mitochondrial activity in an HFpEF rat model.
• To elucidate the molecular mechanisms underlying Empa's impact on SKM in HFpEF.

Main Methods:

• Obese ZSF1 rats (HFpEF model) and lean controls received Empa or standard care for 8 weeks.
• Echocardiography, SKM contractility tests, and mitochondrial function assessments were performed.
• SKM tissue was analyzed for molecular changes.

Main Results:

• Empa treatment improved cardiac function (E/é) and enhanced SKM contractility in HFpEF rats.
• Intramuscular lipid content was reduced, and mitochondrial function, particularly Complex IV, was improved.
• Minimal changes were observed in atrophy-related proteins.

Conclusions:

• Empagliflozin demonstrates beneficial effects on skeletal muscle function and mitochondrial health in a preclinical HFpEF model.
• These findings suggest Empa may mitigate exercise intolerance associated with HFpEF through improved SKM and mitochondrial function.