Differentiation of the plasma metabolite profile detected with 1H-NMR spectroscopy of obese and normal-weight children and adolescents

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 complications. To improve current 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 obesity, since the plasma metabolite profile is reflective of metabolic processes. Aim: To investigate and compare the metabolite profile of obese and normal-weight children detected with 1H-NMR spectroscopy. Methods: Fasting plasma samples of 20 obese (mean age: 13.4 ± 2.2 yrs; mean BMI: 33.6 ± 4.9 kg/m²) and 20 normal-weight children (mean age: 13.5 ± 2.9 yrs; mean BMI: 19.3 ± 2.3 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 standard liquid 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). These 110 variables were compared between obese and normal-weight children using Mann-Whitney U test. OPLS-DA multivariate analysis was applied (SIMCA-P+ 12, Umetrics, Umea, Sweden). Results: The plasma metabolite profiles of obese children could be clearly distinguished from those of normal-weight children. After correction for multiple testing, 19 spectral regions (p value < 4.545 x 10-4) were significantly different in obese compared with normal-weight children. Conclusions: Our findings show a clear differentiation between the plasma metabolite profile of obese and normal-weight children. However, additional research is needed in a larger sample population in order to translate current findings into a clinically meaningful outcome.