early metabolic defects in dexamethasone-exposed and undernourished intrauterine growth restricted rats早期代谢缺陷dexamethasone-exposed和营养不良大鼠宫内生长受限.pdfVIP

Early Metabolic Defects in Dexamethasone-Exposed and Undernourished Intrauterine Growth Restricted Rats 1 1 ´ 1 1 Emmanuel Somm *, Delphine M. Vauthay , Audrey Guerardel , Audrey Toulotte , Philippe Cettour- 1 1 2 1 ¨ 1 ´ 1 Rose , Philippe Klee , Paolo Meda , Michel L. Aubert , Petra S. Huppi , Valerie M. Schwitzgebel 1 Department of Paediatrics, University of Geneva School of Medicine, Geneva, Switzerland, 2 Department of Cell Physiology and Metabolism, University of Geneva School of Medicine, Geneva, Switzerland 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 mg/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, decrea