Adipose tissue gene expression profiling reveals distinct molecular pathways that define visceral adiposity in offspring of maternal protein-restricted rats

Departments of 1 Obstetrics and Gynaecology 2 Medicine 3 Physiology and Pharmacology, Canadian Institutes of Health Research Group in Fetal and Neonatal Health and Development, Children's Health Research Institute and Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada Submitted 30 September 2004 ; accepted in final form 19 November 2004 There is increasing evidence that poor early growth confers an increased risk of type 2 diabetes, hypertension, and other features of the metabolic syndrome in later life. We hypothesized that this may result from poor nutrition during early life exerting permanent effects on the structure and function of key metabolic organ systems. To study the long-term impact of early-life undernutrition on susceptibility to visceral adiposity, we used a rat model of maternal protein restriction (MPR) in which dams were fed a low-protein diet (containing 8% instead of 20% protein in control diet) throughout pregnancy and lactation. MPR offspring were born smaller than controls (offspring of dams on control diet) and in adulthood developed visceral adiposity. We compared the pattern of gene expression in visceral adipose tissue (VAT) between MPR offspring and controls with Affymetrix rat expression arrays. Of the total number of genes and expressed sequence tags analyzed (15,923 probe sets), 9,790 (61.5%) were expressed in VAT. We identified 650 transcripts as differentially expressed 1.5-fold in the VAT of MPR offspring. Gene ontology analysis revealed a global upregulation of genes involved in carbohydrate, lipid, and protein metabolism. A number of genes involved in adipocyte differentiation, angiogenesis, and extracellular matrix remodeling were also upregulated. However, in marked contrast to other rodent models of obesity, the expression of a large number of genes associated with inflammation was reduced in this rat model. Thus visceral adiposity in this early-life programmed rat model is marked by dynamic changes in the transcriptional profile of VAT. Our data provide new insights into the molecular mechanisms that underlie the early-life programming of visceral adiposity. visceral adipose tissue; maternal protein restriction; DNA microarray Address for reprint requests and other correspondence: K. Yang, Children's Health Research Institute, Rm. A5-132, Victoria Research Laboratories- Westminster Campus, 800 Commissioners Road East, London, ON, Canada N6A 4G5 (E-mail: kyang{at}uwo.ca )