title: Catch-up growth following intra-uterine growth-restriction programmes an insulin-resistant phenotype in adipose tissue.
abstract: BACKGROUND
  It is now widely accepted that the early-life nutritional environment is important in determining susceptibility to metabolic diseases. In particular, intra-uterine growth restriction followed by accelerated postnatal growth is associated with an increased risk of obesity, type-2 diabetes and other features of the metabolic syndrome. The mechanisms underlying these observations are not fully understood.
  
  
  OBJECTIVE
  Using a well-established maternal protein-restriction rodent model, our aim was to determine if exposure to mismatched nutrition in early-life programmes adipose tissue structure and function, and expression of key components of the insulin-signalling pathway.
  
  
  METHODS
  Offspring of dams fed a low-protein (8%) diet during pregnancy were suckled by control (20%)-fed dams to drive catch-up growth. This 'recuperated' group was compared with offspring of dams fed a 20% protein diet during pregnancy and lactation (control group). Epididymal adipose tissue from 22-day and 3-month-old control and recuperated male rats was studied using histological analysis. Expression and phosphorylation of insulin-signalling proteins and gene expression were assessed by western blotting and reverse-transcriptase PCR, respectively.
  
  
  RESULTS
  Recuperated offspring at both ages had larger adipocytes (P<0.001). Fasting serum glucose, insulin and leptin levels were comparable between groups but increased with age. Recuperated offspring had reduced expression of IRS-1 (P<0.01) and PI3K p110β (P<0.001) in adipose tissue. In adult recuperated rats, Akt phosphorylation (P<0.01) and protein levels of Akt-2 (P<0.01) were also reduced. Messenger RNA expression levels of these proteins were not different, indicating a post-transcriptional effect.
  
  
  CONCLUSIONS
  Early-life nutrition programmes alterations in adipocyte cell size and impairs the protein expression of several insulin-signalling proteins through post-transcriptional mechanisms. These indices may represent early markers of insulin resistance and metabolic disease risk.
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. lmb81@cam.ac.uk
authors.forename: L M
authors.initials: LM
authors.lastname: Berends
authors.forename: D S
authors.initials: DS
authors.lastname: Fernandez-Twinn
authors.forename: M S
authors.initials: MS
authors.lastname: Martin-Gronert
authors.forename: R L
authors.initials: RL
authors.lastname: Cripps
authors.forename: S E
authors.initials: SE
authors.lastname: Ozanne
mesh_terms: D017667:Adipocytes; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D007328:Insulin; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000473:pathology*; D009765:Obesity / Q000473:pathology*; D010641:Phenotype; D010766:Phosphorylation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; C494923:Akt2 protein, rat; D051057:Proto-Oncogene Proteins c-akt