# E‐cigarette exposure impairs skeletal muscle mitochondrial function in male mice

## TL;DR

E-cigarette vapor harms muscle mitochondria in male mice, similar to tobacco smoke, but through a different biological pathway.

## Contribution

Shows E-cig vapor causes mitochondrial dysfunction in skeletal muscle via AHR-independent mechanisms.

## Key findings

- E-cig vapor reduced mitochondrial respiration in mouse muscle cells and mice.
- Both E-cig and tobacco smoke impaired mitochondrial function in mice, but only tobacco smoke activated the AHR pathway.
- Muscle contractility was unaffected by chronic exposure to either vapor or smoke.

## Abstract

While conventional tobacco‐cigarette smoking continues to decline, e‐cigarette (E‐cig) use is rising, yet its physiological consequences remain poorly characterized. Chronic activation of the aryl hydrocarbon receptor (AHR) by tobacco smoke impairs skeletal muscle mitochondrial function. Here, we evaluated whether E‐cig vapor elicits AHR activation and mitochondrial dysfunction in skeletal muscle. C2C12 mouse myoblasts were exposed to 1% dimethyl sulfoxide (vehicle), 0.02% tobacco‐smoke condensate (TSC), or vape condensate (VC) at 0.006%, 0.06%, and 0.3%. Cell viability, AHR‐pathway gene expression (Ahr, Ahrr, Cyp1a1), and mitochondrial respiration were assessed. Male C57BL/6J mice (12–16 weeks; n = 4–5/group) underwent acute 2‐h or 4‐week exposure to room air, tobacco smoke, or E‐cig vapor. Serum cotinine, gastrocnemius AHR‐pathway genes, muscle contractility, and mitochondrial function were evaluated. In myoblasts, 0.02% TSC and 0.3% VC upregulated Ahrr and Cyp1a1 (p < 0.0001) and reduced complex I state‐3 respiration (p < 0.05) without affecting viability. In mice, acute exposure to tobacco smoke and E‐cig vapor significantly increased serum cotinine (p < 0.0001), but only tobacco‐smoke activated AHR‐pathway. Chronic exposure to tobacco smoke and E‐cig vapor reduced mitochondrial complex I and II state‐3 respiration (p < 0.05), without altering muscle contractile function. These findings suggest that AHR‐independent mechanisms contribute to mitochondrial dysfunction with E‐cig vapor exposure.

E‐cigarette vapor induces skeletal muscle mitochondrial dysfunction through AHR‐independent pathways.