Metabolites involved in Glycolysis and Amino Acid Metabolism are Altered in Short Children Born Small for Gestational Age

BACKGROUND: Later life metabolic dysfunction is a well-recognised consequence of being born Small for Gestational Age (SGA). This study has applied metabolomics to identify whether there are changes in these pathways in pre-pubertal short SGA children and aimed to compare the intracellular and extracellular metabolome in fibroblasts derived from healthy children and SGA children with post-natal growth impairment. METHODS: Skin fibroblast cell lines were established from eight SGA children (age 1.8 -10.3 years) with failure of catch-up growth and from three healthy control children. Confluent cells were incubated in serum free media and the spent growth medium (metabolic footprint) and intracellular metabolome (metabolic fingerprint) were analysed by gas-chromatography mass spectrometry. RESULTS: 19 metabolites were significantly altered between SGA and control cell lines. The greatest fold difference (FD) was seen for alanine (fingerprint FD, SGA: control) 0.3, p=0.01 and footprint FD=0.19, p=0.01), aspartic acid (fingerprint FD=5.21, p=0.01) and cystine (footprint FD=1.66, p=0.02). Network analysis of the differentially expressed metabolites predicted inhibition of insulin and activation of ERK/AKT/PI3K signalling in SGA cells. CONCLUSIONS: This study indicates that changes in cellular metabolism associated with both growth failure and insulin insensitivity are present in pre-pubertal short children born SGA.