Transcript Obese and normal-weight children display a different plasma

Obese and normal-weight children display a different plasma metabolic profile as
1
measured with H-NMR spectroscopy
Bervoets Liene1,2,3, Massa Guy2, Reekmans Gunter3 and Adriaensens Peter3
1Faculty
of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
2Department of Paediatrics, Jessa Hospital, Hasselt, Belgium
3Institute for Materials Research (IMO), Hasselt University, Diepenbeek, Belgium
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 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
obesity.
1H-NMR
investigation and statistical comparison of the plasma metabolic profile of
obese and normal-weight children in order to gain information regarding the involved
biochemical pathways and to define obesity-related biomarkers.
Table 1 | General characteristics of the study population. F: female; M: male; N: native; A:
allochthonous.
There were more boys (p=0.006) and children of allochthonous origin (p=0.002) in the
obese study group. Age was not different between the two groups (p=0.886). BMI was
higher in obese children compared to normal-weight children (p<0.001).
Subjects
81 children between 8 and 18 years
53 overweight or obese
1H-NMR
28 normal-weight
Figure 1 | OPLS-DA score plot of the model discriminating between obese (green) and normalweight (blue) children. The horizontal axis corresponds to between class variability and the
vertical axis to within class variability. R2X=0.81; R2Y=0.76; Q2=0.69
spectroscopy
Multivariate analysis of 1H-NMR data regarding plasma metabolite concentrations
reveals a separation of obese and normal-weight children.
Fasting plasma sample
lipids
(VLDL,LDL)
lactate
13 000 g
4 min
4°C
unsaturated
lipids
200 µl plasma + 600 µl D2O + TSP
proline
arginine
myo-inositol
glucose
NI
α-ketoglutarate
cysteine
asparagine
citrate
Figure 2 | S-line plot for the OPLS-DA model between obese (positive) and normal-weight
(negative) children. The colored scale bar indicates the importance of metabolite variations in
discriminating between obese and normal-weight children.
The obese metabolite profile showed an increase in unsaturated lipids, proline, lactate,
lipids (VLDL and LDL) and a non-identified compound, besides a decrease in glucose,
arginine, myo-inositol, α-ketoglutarate,cysteine, asparagine and citrate
1H-NMR spectroscopy
400 MHz Agilent/Varian Inova spectrometer
Statistical analysis
Differences in general characteristics between the two study groups were analyzed
using the independent samples t test for scale variables and Chi square test for nominal
variables. Statistical significance was assessed at the 5% level. The integration value of
110 spectral regions were normalized to the total integration area (except for TSP,
water, glucose and fructose). Multivariate analysis was performed by means of OPLSDA using SIMCA-P+ 12 (version 12.0, Umetrics, Umeå, Sweden).
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. Obese children have
elevated concentrations of lipids, VLDL, LDL, unsaturated lipids and myo-inositol in their
plasma, suggesting an increased fat synthesis. The additional reduced glucose
concentration suggests a high rate of glucose consumption for fat synthesis.
Furthermore, several metabolites important in energy and amino acid metabolism
differentiate between obese and normal-weight children. Future research will focus on a
large sample population in order to define obesity-related biomarkers.
This study is part of the Limburg Clinical Research Program (LCRP) UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk, Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. Samples are
stored at the University Biobank Limburg (UBiLim).
Contact information: [email protected]