title: Metabolites involved in glycolysis and amino acid metabolism are altered in short children born small for gestational age.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  This study indicates that changes in cellular metabolism associated with both growth failure and insulin insensitivity are present in prepubertal short children born SGA.
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK.|Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK.
authors.forename: Philip G
authors.identifier: 0000-0002-1480-1576
authors.initials: PG
authors.lastname: Murray
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK.|Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK.
authors.forename: Imogen
authors.initials: I
authors.lastname: Butcher
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK.|Manchester Centre for Integrative Systems Biology, University of Manchester, Manchester, UK.|School of Biosciences, University of Birmingham, Birmingham, UK.
authors.forename: Warwick B
authors.initials: WB
authors.lastname: Dunn
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK.|Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK.
authors.forename: Adam
authors.identifier: 0000-0002-1950-7325
authors.initials: A
authors.lastname: Stevens
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK.|Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK.
authors.forename: Reena
authors.initials: R
authors.lastname: Perchard
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK.|Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hanson
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK.|Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Whatmore
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK.|Maternal and Fetal Health Research Centre, University of Manchester, Manchester, UK.
authors.forename: Melissa
authors.initials: M
authors.lastname: Westwood
authors.affiliation: Institute of Human Development, University of Manchester, Manchester, UK.|Centre for Paediatrics and Child Health, University of Manchester, Manchester, UK.
authors.forename: Peter E
authors.identifier: 0000-0003-1225-4537
authors.initials: PE
authors.lastname: Clayton
mesh_terms: D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005865:Gestational Age; D006019:Glycolysis; D006130:Growth Disorders / Q000097:blood* / Q000150:complications; D006720:Homozygote; D006801:Humans; D007223:Infant; D007236:Infant, Small for Gestational Age; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D009154:Mutation; D012867:Skin / Q000378:metabolism
chemical_list: D000596:Amino Acids; D007328:Insulin; D001224:Aspartic Acid; D000409:Alanine