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

IF 2.4 4区医学 Q2 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH

Tobacco Induced Diseases Pub Date : 2026-09-05 eCollection Date: 2026-01-01 DOI:10.18332/tid/226887

Zijing Li, Daoyuan Li, Yuli Huang, Yushang Liu, Xinye Ouyang, Yufei Xu, Wenjuan Wu, Yanbiao Zhong, Maoyuan Wang

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引用次数: 0

Abstract

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.

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香烟毒物对肌肉减少型肥胖的影响：计算机网络毒理学和分子动力学研究。

摘要：肌少性肥胖（Sarcopenic obesity， SO）是一种以肌肉质量减少、肌肉力量下降、脂肪过度积累为特征的老年代谢综合征。尼古丁和煤焦油破坏骨骼肌稳态和脂质代谢。本研究旨在通过集成的计算机方法阐明尼古丁和煤焦油引发肌肉减少性肥胖的相关分子机制。方法：这项计算机研究于2026年5月使用公开的数据库和计算平台进行。从GeneCards和OMIM中检索尼古丁、煤焦油和SO的靶标，并使用Venny识别靶标的交集。KEGG富集检测关键通路。通过STRING构建蛋白-蛋白相互作用（PPI）网络，并利用Cytoscape中的最大团中心性（maximum Clique Centrality， MCC）算法对10个核心基因进行排序。三个GEO转录组数据集（GSE290570, GSE262419, GSE226045）用于交叉验证尼古丁、煤焦油和SO相关的差异表达基因。使用CB-DOCK2进行尼古丁与5种核心蛋白的分子对接，并使用GROMACS进行50 ns分子动力学模拟，通过均方根偏差（RMSD）、均方根波动（RMSF）、旋转半径（Rg）、溶剂可及表面积（SASA）和氢键分析来评估复合物的稳定性。结果：确定了20个交叉靶点。富集的通路包括MAPK、PI3K/Akt、p53、胆固醇代谢和铁下垂。五个核心基因（IL1β, IGF1, FGF2， CTNNB1和CXCL12）通过GEO转录组数据交叉验证。烟碱与CTNNB1、CXCL12、IGF1和il - 1β稳定结合，结合能在-3.3 ~ -4.2 kcal/mol之间，而烟碱与FGF2的结合能为正值（0.7）。MD模拟证实，所有配合物在整个50 ns的轨迹中都保持了结构稳定性。结论：尼古丁和煤焦油可能调节核心基因以及炎症和代谢相关途径，促进SO的进展。本研究为预防烟草暴露性SO提供了理论参考。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tobacco Induced Diseases SUBSTANCE ABUSE-PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH

CiteScore

5.30

自引率

5.40%

发文量

审稿时长

12 weeks

期刊介绍： Tobacco Induced Diseases encompasses all aspects of research related to the prevention and control of tobacco use at a global level. Preventing diseases attributable to tobacco is only one aspect of the journal, whose overall scope is to provide a forum for the publication of research articles that can contribute to reducing the burden of tobacco induced diseases globally. To address this epidemic we believe that there must be an avenue for the publication of research/policy activities on tobacco control initiatives that may be very important at a regional and national level. This approach provides a very important "hands on" service to the tobacco control community at a global scale - as common problems have common solutions. Hence, we see ourselves as "connectors" within this global community. The journal hence encourages the submission of articles from all medical, biological and psychosocial disciplines, ranging from medical and dental clinicians, through health professionals to basic biomedical and clinical scientists.