Impact of cigarette toxicants on sarcopenic obesity: An in silico network toxicology and molecular dynamics study.

INTRODUCTION: Sarcopenic obesity (SO) is a geriatric metabolic syndrome characterized by muscle mass loss, muscle strength decline, and excessive fat accumulation. Nicotine and coal tar disrupt skeletal muscle homeostasis and lipid metabolism. This study aims to elucidate the relevant molecular mechanisms by which nicotine and coal tar trigger sarcopenic obesity using an integrated in silico approach. METHODS: This in silico study was conducted in May 2026 using publicly available databases and computational platforms. Targets for nicotine, coal tar, and SO were retrieved from GeneCards and OMIM, and the intersection of targets was identified using Venny. KEGG enrichment was performed to detect key pathways. A protein-protein interaction (PPI) network was constructed via STRING, and the top 10 core genes were ranked by the Maximal Clique Centrality (MCC) algorithm in Cytoscape. Three GEO transcriptomic datasets (GSE290570, GSE262419, GSE226045) were used to cross-validate differentially expressed genes related to nicotine, coal tar, and SO. Molecular docking between nicotine and five core proteins was performed using CB-DOCK2, and 50 ns molecular dynamics simulations with GROMACS were used to assess complex stability via root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and hydrogen-bond analysis. RESULTS: Twenty intersection targets were identified. Enriched pathways included MAPK, PI3K/Akt, p53, cholesterol metabolism, and ferroptosis. Five core genes (IL1β, IGF1, FGF2, CTNNB1, and CXCL12) were cross-validated by GEO transcriptomic data. Nicotine bound stably to CTNNB1, CXCL12, IGF1, and IL1β with binding energies ranging from -3.3 to -4.2 kcal/mol, whereas FGF2 showed a positive value (0.7). MD simulations confirmed that all complexes maintained structural stability throughout the 50 ns trajectory. CONCLUSIONS: Nicotine and coal tar may regulate core genes and inflammation- and metabolism-related pathways to promote SO progression. This study provides theoretical references for preventing tobacco exposure-induced SO.