Metabolites involved in glycolysis and amino acid metabolism are altered in short children born small for gestational age.

Abstract:

BACKGROUND:Later life metabolic dysfunction is a well-recognized consequence of being born small for gestational age (SGA). This study has applied metabolomics to identify whether there are changes in these pathways in prepubertal short SGA children and aimed to compare the intracellular and extracellular metabolome in fibroblasts derived from healthy children and SGA children with postnatal growth impairment. METHODS:Skin fibroblast cell lines were established from eight SGA children (age 1.8-10.3 y) 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 analyzed by gas-chromatography mass spectrometry. RESULTS:Nineteen 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 as well as growth (ERK) signaling in SGA cells. CONCLUSION:This study indicates that changes in cellular metabolism associated with both growth failure and insulin insensitivity are present in prepubertal short children born SGA.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Murray PG,Butcher I,Dunn WB,Stevens A,Perchard R,Hanson D,Whatmore A,Westwood M,Clayton PE

doi

10.1038/pr.2016.72

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

299-305

issue

2

eissn

0031-3998

issn

1530-0447

pii

pr201672

journal_volume

80

pub_type

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