Gas chromatography-mass spectrometry pilot study to identify volatile organic compound biomarkers of childhood obesity with dyslipidemia in exhaled breath

Abstract

Objectives: Childhood obesity affects multiple organs in the body and is associated with both significant morbidity and ultimately premature mortality. Childhood obesity, especially dyslipidemia, can lead to early atherosclerosis and premature cardiovascular disease (CVD) in adulthood. The detection of exhaled volatile organic compounds (VOCs) in the breath offers the opportunity for the discovery of novel disease-specific biomarkers. This study aimed to identify VOCs that correlate with childhood obesity accompanied by dyslipidemia.

Methods: A total of 82 overweight or obese children between the ages of 8 and 12 years were recruited from the exercise on obesity adolescents in Peking (EXCITING) study (NCT04984005). The breath VOCs of the participants were measured by gas chromatography-mass spectrometry (GC-MS). The classification was performed using principal component analysis (PCA) of the relative abundance of VOCs. The difference between the obese and overweight groups with or without dyslipidemia was analyzed.

Results: Among the 82 children, 25 were overweight, of whom 10 had dyslipidemia. The other 57 children were obese, and 17 of them had dyslipidemia. Obese children with dyslipidemia had higher triglycerides and elevated non-high-density lipoprotein-cholesterol compared to overweight children without dyslipidemia. We confirmed 13 compounds based on database well matches (average score > 80) for mass spectra and refractive index. These 13 VOCs were grouped into three chemical functional groups: saturated hydrocarbons, aromatic hydrocarbons and unsaturated aldehydes. For obese children with dyslipidemia, the PCA scatter plot of the three chemical groups was obviously separated from the other groups. Some of the candidates, including heptadecane, naphthalene, and cis-6-nonnenol, were significantly higher in obese children with dyslipidemia than in overweight groups with or without dyslipidemia.

Conclusion: A suite of VOCs from three chemical function groups, saturated hydrocarbons, aromatic hydrocarbons, and unsaturated aldehydes, were separated in the obese children with dyslipidemia. Heptadecane, naphthalene, and cis-6-nonenol were significantly elevated in obese children with dyslipidemia. Our findings underscore the potential value of the candidate VOCs for future risk categorization.

Keywords: childhood; dyslipidemia; obesity; volatile organic compounds.

Figure 1

The schematic flowchart of the study design and procedures of the present study. GC-MS: gas chromatography-mass spectroscopy.

Figure 2

Principal component analysis of certain categories of VOCs and a scatter plot showing separation among obesity and overweight participants with or without dyslipidemia. (A) Saturated hydrocarbons, (B) aromatic hydrocarbons, and (C) unsaturated aldehydes. VOCs: volatile organic compounds; PCA: principal component analysis.

Figure 3

Relative levels of specific VOCs in obese and overweight children with or without dyslipidemia. (A) Saturated hydrocarbons, including heptadecane, undecane, dodecane, tridecane, tetradecane, and pentadecane. (B) Aromatic hydrocarbons, including naphthalene, methylnaphthalene, benzene, 1,2,3,4-tetramenthyl, and phenol. (C) Unsaturated aldehydes, including cis-6-nonenol, 2-octenal, and d-limonene. *P < 0.05; **P < 0.01. VOCs: volatile organic compounds.

Figure 4

Selected extraction chromatogram of the representative VOCs that distinguish between obese and overweight participants with or without dyslipidemia. (A) Heptadecane, (B) naphthalene, (C) cis-6-nonenol. VOCs: volatile organic compounds.