BRAIN AND PERIPHERAL RENIN-ANGIOTENSIN SISTEM ACTIVITY IN A MODEL OF OBESITY PROGRAMMING BY REDUCED LITTER SIZE

• Grant number: 11/24148-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2012
• End date: January 31, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: José Antunes Rodrigues
• Grantee: Andre de Souza Mecawi
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 13/23057-8 - Transcriptome analysis of the paraventricular and arcuate nucleus in a model of neonatal obesity, BE.EP.PD

Abstract

The metabolic programming can be defined as exposure to stimulus during a critical period of the animal development (when several organs are still developing and are sensitive to changes of the environment) which will result in effects in the adulthood, when the central nervous system loses your plasticity and the functional capacity is fixed. The manipulation of litter size in the rodent early life is one of the metabolic neonatal programming model used, which results in greater weight gain of the animals in small litters, a phenotype that persists in the adulthood. Moreover, several studies have demonstrated the importance of the renin-angiotensin system (RAS) in the pathophysiology of obesity and its correlation with cardiovascular diseases and, especially, hypertension. However, no correlation was established between the RAS activity and the development of the obesity programming by reducing the litter size, as well as the possible RAS impact in electrolyte homeostasis and cardiovascular systems in these obesity programming model.Thus, using the model of reduced litter size, this study aims to investigate the involvement of the renin-angiotensin system on the pathophysiology of neonatal obesity and it's repercussions on the activity of the circulating, brain and adipose renin-angiotensin system. For this purpose, male Wistar rats will be kept in litters with 3 or 8 pups per female. After weaning, the body weight gain, food and fluid intake, urinary volume and blood pressure will be evaluated weekly. The animals will be decapitated at 21 or 60 days old and the blood will be collected for measurements of the RAS components; the hypothalamus, aorta and adipose tissue will be collected to verify the gene expression of the RAS receptors (AT1, AT2 and Mas). In addition, we will use the aorta to study the vascular reactivity to several drugs and hormones; in the kidneys, liver, lung and adipose tissue we will verify the gene expression of the main RAS enzymes [renin, angiotensinogen and angiotensin-converting enzyme (ACE)]. Also, a group of animals with 60 days old we will study the baroreflex sensitivity to hypo or hypertensive drugs; other group will be treated with AT1 antagonist receptor or ACE inhibitors since weaning to adulthood, to study the same parameters (besides the concentration of triglycerides, leptin and insulin in the blood) to verify the role of the rennin-angiotensin system in the pathophysiology of obesity programming in a model of reduced litter size.