Abstract
The aim of this study was to compare changes in the metabolite levels of ex-smokers and nonsmokers using a metabolomics approach, accounting for the weight gain in ex-smokers. Volunteer ex-smokers and nonsmokers were recruited from two cohorts Shijingshan (174) and Xishan (78), respectively, at a 1 : 1 ratio for age and sex. Nontargeted metabolomics was performed on the volunteers' blood samples using liquid chromatography-mass spectrometry, and multivariate statistical analysis was performed using principal component analysis and orthogonal partial least squares discriminant analysis. Enrichment analysis was used to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with differential metabolites and weighted gene co-expression network analysis and maximal correlation coefficient (MCC) algorithms were used to identify key metabolites. The results revealed no significant differences between the distribution of blood metabolite levels in the ex-smokers and nonsmokers. The biosynthesis of valine, leucine, and isoleucine was determined to be associated with differential metabolites, and five key metabolites were identified. Further analysis revealed differences in weight gain and regained metabolite levels in ex-smokers, and 10 differential metabolites were identified that may be associated with weight gain in ex-smokers. These findings suggest that quitting smoking restores metabolites to almost normal levels and results in weight gain. The identified key metabolites and metabolic pathways may also provide a basis for clinical studies.