Beta-Hydroxybutyrate Inhibits Bronchial Smooth Muscle Contraction

Area of Science:

• Respiratory Medicine
• Metabolic Physiology
• Pharmacology

Background:

• Asthma involves airway inflammation and smooth muscle constriction, with current treatments not always sufficient for severe cases.
• Therapeutic ketosis, increasing ketone bodies, is emerging as a potential asthma therapy.
• Ketone bodies influence cellular pathways relevant to asthma pathophysiology.

Purpose of the Study:

• To investigate the effects of beta-hydroxybutyrate (BHB) on airway smooth muscle contraction in asthma.
• To determine if BHB can mitigate bronchoconstriction in preclinical asthma models.

Main Methods:

• Utilized human bronchial smooth muscle cells (in vitro) and mouse precision-cut lung slices (PCLS) (ex vivo).
• Assessed the impact of BHB on histamine-induced bronchoconstriction.
• Examined the role of free fatty acid receptor 3 (FFAR3) in BHB's effects.

Main Results:

• BHB significantly reduced contraction in human bronchial smooth muscle cells, mediated by FFAR3 activation.
• BHB inhibited airway narrowing and cellular extrusion in mouse PCLS.
• These findings demonstrate BHB's ability to suppress smooth muscle contraction and mitigate asthma-related bronchoconstriction.

Conclusions:

• Bronchial smooth muscle is a cellular target for therapeutic ketosis in asthma.
• BHB demonstrates therapeutic potential in preclinical asthma models by reducing airway smooth muscle hyperresponsiveness.
• These findings support further investigation of ketone bodies as an alternative asthma therapy.