Impact of secondhand smoke and e-cigarette aerosol on overweight or obesity in adolescents: a network pharmacology and toxicology study.

Abstract

Objective: Rising childhood obesity is a global concern, with environmental tobacco exposure as a potential risk factor. However, the mechanisms linking secondhand smoke and e-cigarette aerosol to adolescent obesity remain unclear.

Methods: We analyzed data from 968 participants aged 3- 19 years in the NHANES 2017- 2020 cycles. Passive exposure was assessed using self-reported household exposure and objectively measured serum cotinine levels. Multivariate logistic regression was used to evaluate the associations between exposure categories and overweight/obesity status. Cotinine-related molecular targets were identified through network pharmacology and toxicology analyses, with protein-protein interaction networks, enrichment analyses, and molecular docking used to explore relevant pathways.

Results: Compared with unexposed individuals, participants exposed to both secondhand smoke and e-cigarette aerosols had significantly greater odds of overweight or obesity (adjusted odds ratio [aOR] = 3.9; 95% CI: 1.4-11.0; p = 0.009). Serum cotinine levels were also positively associated with obesity risk in a dose-dependent manner, with those in the highest quartile (Q4) showing aOR = 3.8 (95% CI: 2.1-6.8; p < 0.001) compared with those in Q1. Network analyses identified CHRNA2 and CHRNB2 as key targets involved in cholinergic signaling and metabolic regulation. Cotinine demonstrated strong binding affinity to these targets in molecular docking, supporting its potential biological activity beyond being a nicotine biomarker.

Conclusion: Passive nicotine exposure is significantly associated with overweight or obesity among adolescents, and cotinine may be involved in relevant biological pathways related to energy regulation. These findings may inform future research and preventive strategies.