Examination of serum metabolome altered by cigarette smoking identifies novel metabolites mediating smoking‐BMI association

Abstract

Objective The authors hypothesize that an untargeted metabolomics study will identify novel mechanisms underlying smoking‐associated weight loss. Methods This study performed cross‐sectional analyses among 1,252 participants in the Bogalusa Heart Study and assessed 1,202 plasma metabolites for mediation effects on smoking‐BMI associations. Significant metabolites were tested for associations with smoking genetic risk scores among a subset of participants (n = 654) with available genomic data, followed by direction dependence analysis to investigate causal relationships between the metabolites and smoking and BMI. All analyses controlled for age, sex, race, education, alcohol drinking, and physical activity. Results Compared with never smokers, current and former smokers had a 3.31‐kg/m2 and 1.77‐kg/m2 lower BMI after adjusting for all covariables, respectively. A total of 22 xenobiotics and 94 endogenous metabolites were significantly associated with current smoking. Eight xenobiotics were also associated with former smoking. Forty metabolites mediated the smoking‐BMI associations, and five showed causal relationships with both smoking and BMI. These metabolites, including 1‐oleoyl‐GPE (18:1), 1‐linoleoyl‐GPE (18:2), 1‐stearoyl‐2‐arachidonoyl‐GPE (18:0/20:4), α‐ketobutyrate, and 1‐palmitoyl‐GPE (16:0), mediated 26.0% of the association between current smoking and BMI. Conclusions This study cataloged plasma metabolites altered by cigarette smoking and identified five metabolites that partially mediated the association between current smoking and BMI.

Role of untargeted omics biomarkers of exposure and effect for tobacco research

“…No features were statistically different among the groups, suggesting the application of metabolomics in tobacco cessation studies. A larger study of 1252 participants incorporating the assessment of smoking-related weight loss where eight plasma xenobiotics were associated with former smoking and 22 xenobiotics and 94 endogenous metabolites were significantly associated with current smoking, including α -ketobutyrate, homoarginine, β -cryptoxanthin, 1-linoleoyl-GPE (18:2), 1-Palmitoyl-GPE (16:0), 1-Stearoyl-2-arachidonoyl-GPE (18:0/20:40 and 2 sphingomyelins [ 95 ].…”

Challenges in the Metabolomics-Based Biomarker Validation Pipeline

“…Some examples of environmental factors influencing the metabolome include s ing and diet. Cigarette smoking has been found to alter the metabolome and metab associated, with smoking having also been found to be associated with body mass i (BMI) [19]. Zhang et al discovered that a total of 168 metabolites were altered d smoking, and 40 were metabolites that mediate the smoking-BMI association [19] known metabolites belonged to compound groups, lipids, xenobiotics, amino acids more [19].…”

“…Cigarette smoking has been found to alter the metabolome and metab associated, with smoking having also been found to be associated with body mass i (BMI) [19]. Zhang et al discovered that a total of 168 metabolites were altered d smoking, and 40 were metabolites that mediate the smoking-BMI association [19] known metabolites belonged to compound groups, lipids, xenobiotics, amino acids more [19]. A small difference in diet, such as an increased consumption of whole whe white bread, can result in differences in betaine and cytosine levels [20].…”

“…Zhang et al discovered that a total of 168 metabolites were altered due to smoking, and 40 were metabolites that mediate the smoking-BMI association [19]. The known metabolites belonged to compound groups, lipids, xenobiotics, amino acids, and more [19]. A small difference in diet, such as an increased consumption of whole wheat or white bread, can result in differences in betaine and cytosine levels [20].…”

Untargeted metabolomics unravel serum metabolic alterations in smokers with hypertension

“…They showed increased bile acid metabolites, especially taurodeoxycholic acid in the colon of mice after smoke exposure (Bai et al, 2022). In addition, the serum metabolome of smoking patients has been identified to differ from that of non-smoking individuals (Xu et al, 2013;Zhang et al, 2022). For instance, Xu et al indicated that compared with former and non-smokers, in male current smokers, the concentrations of four unsaturated diacyl-phosphatidylcholines (PCs) and five amino acids (arginine, aspartate, glutamate, ornithine and serine) were increased, while three saturated diacyl-PCs, one lysoPC and four acyl-alkyl-PCs, as well as kynurenine showed lower content.…”