Transcriptome analysis of the paraventricular and arcuate nucleus in a model of neonatal obesity

Abstract

Obesity is a multisystemic disorder characterized by increased percentage of white adipose tissue, and generally associated to peripheral and central resistance to insulin and leptin. These hormones act on the brain, especially in the paraventricular (PVN) and arcuate (ARH) hypothalamic nuclei, regulating energy metabolism and sympathetic tonus (including arterial pressure changes). Thus, both PVN and ARH are crucial areas for the integrated neuroendocrine control of energy and cardiovascular balance. Consequently, they are central targets nuclei to study the development of obesity and associated autonomic and cardiovascular disorders (including hypertension). The neonatal overfeeding (by reducing litter size) and undernutrion (by increasing litter size) are important neonatal models of obesity in adulthood, and have been exploited increasingly in order to understand the epigenetic origins of programmed obesity in adulthood. In this model, the animals subjected to reduced litter size showed high levels of plasma insulin and leptin, hypothalamic resistance to these hormones, increased sympathetic activity and hypertension in adulthood. Thus, the aim of this work is to characterize the changes in global gene expression by means of RNA sequencing technique in the PVN and ARH from obese animals due to neonatal overfeeding or undernutrion. We expect that this technique will allow us to build a database of PVN and ARH of obesity rats, from which new molecular targets can be carefully chosen for the study of the development of obesity and associated autonomic and cardiovascular dysfunctions. (AU)