AT1 receptor blockade abolishes metabolic and cardiovascular programming effects of neonatal obesity and undernutrition (1085.5)

Abstract

The variation of litter size from rodents in the early days of life, which results in neonatal overfeeding or undernutrition, is a very useful model for the obesity study since programs the animals to become obese adults. Moreover, several studies have demonstrated the importance of the angiotensin II (ANG II) in the pathophysiology of obesity and its correlation with cardiovascular diseases. Thus, we aimed to study the role of type 1 ANG II receptors (AT1) on metabolic and cardiovascular effects induced by neonatal obesity or undernutrion programming. For this, the litters were divided into 3 groups: Normal Litter (NL, 10 pups), Small Litter (SL, 3 pups) and Large Litter (LL, 16 pups). The reduction and increment of the litter size increased and decreased , respectively, the body weight (BW) gain in SL (~25%) and LL (~19%) groups, at the weaning (21st day). Despite adult (60 days) SL rats remained with elevated BW, no differences were observed between LL and NL groups. Plasma ANG II levels are higher in both SL (~40%) and LL (~120%) groups in relation to NL at the weaning, with no differences in the adulthood. Both SL and LL groups showed an increase in visceral adipose tissue (~34 and 19%), obesity Lee index (~4 and 3%), and mean arterial pressure (~12 and 10%) in relation to the NL group, respectively. The treatment with losartan (AT1 receptor antagonist) in the drinking water (~ 8 mg / kg / day) from 30 to 60 days of age reduced the visceral adipose tissue weight, Lee index and mean arterial pressure from SL and NL groups. Our data suggest that AT1 receptors are essential for the programming of obesity and hypertension due to neonatal overnutrition or undernutrition.Grant Funding Source: Supported by FAPESP