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Catch-up growth following intra-uterine growth-restriction programmes an insulin-resistant phenotype in adipose tissue.

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Berends, LM 
Fernandez-Twinn, DS 
Martin-Gronert, MS 
Cripps, RL 
Ozanne, SE 


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. AIM: 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. CONCLUSION: 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.



Adipocytes, Adipose Tissue, Animals, Blotting, Western, Body Weight, Diabetes Mellitus, Type 2, Female, Fetal Development, Fetal Growth Retardation, Gene Expression, Insulin, Insulin Resistance, Male, Metabolic Syndrome, Obesity, Phenotype, Phosphorylation, Pregnancy, Prenatal Exposure Delayed Effects, Proto-Oncogene Proteins c-akt, Rats, Rats, Wistar

Journal Title

Int J Obes (Lond)

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Springer Science and Business Media LLC
Biotechnology and Biological Sciences Research Council (BB/F015364/1)
British Heart Foundation (None)
British Heart Foundation (None)
Medical Research Council (MC_UU_12012/4)
Biotechnology and Biological Sciences Research Council (BB/E00797X/1)
Medical Research Council (G0600717)
Medical Research Council (MC_PC_12012)
Medical Research Council (G0600717/1)