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Title

Early metabolic defects in dexamethasone-exposed and undernourished intrauterine growth restricted rats

Authors
Toulotte, Audrey
Cettour-Rose, Philippe
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Published in PLOS ONE. 2012, vol. 7, no. 11, p. e50131
Abstract Poor fetal growth, also known as intrauterine growth restriction (IUGR), is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious "metabolic programming." In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 µg/kg/day, DEX) or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN). Physiological (glucose and insulin tolerance), morphometric (automated tissue image analysis) and transcriptomic (quantitative PCR) approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming.
Keywords Adipose Tissue/growth & development/metabolismAnalysis of VarianceAnimalsBlood Glucose/metabolismBlotting, WesternBody Weights and MeasuresC-Peptide/bloodCorticosterone/bloodDNA Primers/geneticsDexamethasone/adverse effectsFemaleFetal Growth Retardation/metabolismGene Expression ProfilingInsulin/bloodInsulin Resistance/physiologyIslets of Langerhans/growth & development/metabolism/pathologyLeptin/bloodMalnutrition/metabolismPregnancyPrenatal Exposure Delayed Effects/metabolismRadioimmunoassayRatsRats, Sprague-DawleyReal-Time Polymerase Chain Reaction
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PMID: 23166830
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Research groups Etude des altérations du gène ATM dans divers cancers de l'enfant (178)
L'imagerie cérébrale (184)
Couplage cellulaire et connexines (136)
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SOMM, Emmanuel Paul et al. Early metabolic defects in dexamethasone-exposed and undernourished intrauterine growth restricted rats. In: PLOS ONE, 2012, vol. 7, n° 11, p. e50131. https://archive-ouverte.unige.ch/unige:28598

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Deposited on : 2013-06-17

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