Obese and normal-weight children display a different plasma metabolic profile as measured with 1H-NMR spectroscopy

Abstract

Background: Childhood obesity is a major health problem worldwide. Obese children are at high risk to develop co-morbidities such as cardiovascular dysfunction, type 2 diabetes, pulmonary, hepatic and renal complications1. To improve current prevention and treatment strategies for childhood obesity, a proper understanding of obesity-related pathophysiological mechanisms is required. Metabolomics is increasingly used as a tool for the study of obesity2. Aim: To investigate and compare the plasma metabolic profile of obese and normal-weight children as measured with 1H-NMR spectroscopy. Methods: Fasting plasma samples of 53 obese (mean age: 13.1 ± 2.2 yrs; mean BMI: 32.0 ± 4.5 kg/m²) and 28 normal-weight children (mean age: 13.1 ± 3.1 yrs; mean BMI: 18.9 ± 2.4 kg/m²) between 8 and 18 years of age were analysed by means of 1H-NMR spectroscopy. The 1H-NMR spectra were recorded on a 400 MHz Varian Inova spectrometer operating at 9.4 Tesla with a liquid-state PFG probe. Slightly T2-weighted spectra were acquired using a CPMG pulse sequence with water suppression. Spectra are phased manually, baseline corrected, and referenced to trimethylsilyl-2,2,3,3-tetradeuteropropionic acid (TSP) resonance at 0.015 ppm. The integration values of 110 spectral regions were normalized to the total integral area (except for TSP, water, glucose and fructose). Univariate analysis was performed by means of independent samples t test with correction for multiple testing by the Benjamini-Hochberg method. In addition, multivariate analysis by means of PCA and OPLS-DA was performed using SIMCA-P+ 12 (version 12.0, Umetrics, Umeå, Sweden). Results: The plasma metabolic profiles of obese children could be clearly distinguished from those of normal-weight children with a sensitivity of 100% and specificity of 93.9%. After correction for multiple testing, we observed 36 spectral regions to be significantly (p < 4.6 x 10-4) altered in obese children. Obese children showed higher levels of lipids (VLDL and LDL), unsaturated lipids, lactate and proline, and lower levels of citrate, asparagine, cysteine, α-ketoglutarate, myo-inositol, glucose and arginine as compared to normal-weight children. Conclusion: To our knowledge, this is the first study in which 1H-NMR spectroscopy is used as a tool to study childhood obesity. Our findings show that obese children clearly display a different plasma metabolic profile as compared to normal-weight children. In future, longitudinal research on a large sample population is needed in order to enable the discovery of obesity-related biomarkers.

1. l'Allemand-Jander D: Clinical diagnosis of metabolic and cardiovascular risks in overweight children: early development of chronic diseases in the obese child. Int J Obes (Lond) 2010;34(Suppl 2):S32-S36. 2. Zhang A, Sun H and Wang X. Power of metabolomics in biomarker discovery and mining mechanisms of obesity. Obes Rev 2013;14(4):344-349.