Exercise Ameliorates Atherosclerosis via Up-Regulating Serum β-Hydroxybutyrate Levels

Area of Science:

• Cardiovascular Science
• Metabolic Disorders
• Exercise Physiology

Background:

• Atherosclerosis is a leading cause of cardiovascular death, driven by inflammation, metabolic disorders, and unhealthy lifestyles.
• While exercise is a known intervention for atherosclerosis, its underlying mechanisms remain unclear.
• Sedentary lifestyles have exacerbated the global atherosclerosis epidemic.

Purpose of the Study:

• To investigate the mechanisms by which exercise inhibits atherosclerosis progression.
• To explore the role of serum beta-hydroxybutyric acid (BHB) in exercise-induced cardioprotection.
• To evaluate BHB as a potential therapeutic agent for atherosclerosis.

Main Methods:

• ApoE-/- mice on a Western diet underwent 12 weeks of treadmill exercise.
• Serum BHB levels were measured post-exercise.
• In vivo and in vitro studies assessed BHB's effects on lipid accumulation, cholesterol transporters (ABCA1, ABCG1, SR-BI), and autophagy in macrophages and atherosclerotic plaques.

Main Results:

• Exercise training significantly reduced lipid accumulation and foam cell formation in mice.
• Exercise led to increased serum BHB levels.
• BHB treatment enhanced cholesterol transporter expression, reduced lipid accumulation, and ameliorated autophagy in macrophages and plaques.

Conclusions:

• Increased serum BHB is a key mechanism mediating the anti-atherosclerotic effects of exercise.
• BHB promotes cholesterol efflux through enhanced transporter activity and autophagy.
• BHB represents a promising therapeutic strategy for atherosclerosis, particularly for patients unable to exercise.