Gas chromatography-mass spectrometry (GC-MS) metabolomics is unique from other ”omics” in its capacity to efficiently decipher systems biology because of its proximity to phenotype. We established a primate model of in utero exposure to a high-fat (HF) maternal diet leading to fetal fatty liver and demonstrated that an altered fetal epigenomic profile accompanies persistent differential reprogrammed gene expression; reversal of the maternal diet partially abrogates these effects. Given these observations, we aimed to characterize the fetal metabolic spectral footprint and identify candidate biomarker(s) associated with the development of obesity.
Pregnant macaques were fed control (n 22) or HF (n 33) diet for up to 4 years, then reverted from HF to control diet in yr5 (n 7). Serum from neonates (e130) or juvenile (1 yr) offspring generated comprehensive spectral footprints from GC/LC-MS. Multivariate data was analysed with SIMCA-P software (Umetrics) and data were visualized in reduced planar space via principal component analysis with projection onto latent structures with partial least squares-discriminate analysis. Using this reduced data set, significance was derived among candidate metabolites (ANOVA and comparative t-tests).
Of >200 GC-MS identified metabolites, 90 metabolites were chosen for further analysis after meeting QC standards. Observed fetal phenotypic differences were accompanied by an altered spectral footprint of 15 metabolites at a p<.005. Despite ongoing obesity, dams resuming a control diet partially reverted their offsprings metabolite profile to a semi-restorative spectrum with a persistent single metabolite (RT_m/z 18.69_217). Analysis of contributing metabolites revealed two of novel characteristic retention time and mass (7.03_103 & 7.07_159 p<.01).
Collectively, we demonstrate that in utero exposure to a HF diet alters the fetal epigenome to parlay a characteristic metabolic spectral footprint. Application of metabolomics identified putative biomarkers for obesity detectable in neonatal primates.
© 2008 Mosby, Inc. Published by Elsevier Inc. All rights reserved.