E-cigarette exposure impairs skeletal muscle mitochondrial function in male mice

Area of Science:

• Biochemistry
• Toxicology
• Exercise Physiology

Background:

• Conventional smoking declines as e-cigarette use rises, necessitating research into e-cigarette physiological effects.
• Tobacco smoke activates the aryl hydrocarbon receptor (AHR), impairing skeletal muscle mitochondrial function.
• The impact of e-cigarette vapor on AHR signaling and skeletal muscle mitochondria is poorly understood.

Purpose of the Study:

• To investigate if e-cigarette vapor activates the AHR pathway in skeletal muscle.
• To determine the effects of e-cigarette vapor on skeletal muscle mitochondrial function.
• To compare the effects of e-cigarette vapor and tobacco smoke on AHR signaling and mitochondrial health.

Main Methods:

• Exposed C2C12 mouse myoblasts and C57BL/6J mice to tobacco-smoke condensate (TSC) or vape condensate (VC).
• Assessed AHR-pathway gene expression (Ahr, Ahrr, Cyp1a1), cell viability, and mitochondrial respiration in myoblasts.
• Measured serum cotinine, AHR-pathway genes, muscle contractility, and mitochondrial function in mice after acute and chronic exposures.

Main Results:

• Both TSC and VC upregulated AHR-pathway genes and reduced mitochondrial complex I respiration in myoblasts.
• Acute exposure to tobacco smoke and e-cigarette vapor increased serum cotinine in mice.
• Chronic exposure to both substances reduced mitochondrial complex I and II respiration, but only tobacco smoke activated the AHR pathway.

Conclusions:

• E-cigarette vapor exposure leads to skeletal muscle mitochondrial dysfunction.
• This dysfunction appears to be mediated by AHR-independent mechanisms.
• Findings highlight distinct pathways of toxicity between e-cigarettes and conventional tobacco smoke.