Efeito da superalimentação neonatal sobre a função adrenal e o desenvolvimento da microesteatose hepática em ratos adultos

Abstract

Nutritional and hormonal status at early phases of development are related to epigenetic changes, promoting disease development. Childhood overweight is related with late obesity, insulin resistance and higher cardiometabolic risk. Rats overfed during lactation show higher visceral adiposity, hyperphagia, leptin resistance and hypertension in adulthood. Previously, we demonstrated that neonatal hyperleptinemia is associated with adrenal medullary hyperfunction and liver steatosis at adulthood. Here, we evaluated the adrenal function and liver tissue of adult obese rats that were overfed during lactation. To induce early overfeeding, the litter size was reduced from ten to three male pups at the third day of lactation until weaning (SL). Control group had ten rats per litter (NL). After weaning, rats had free access to standard diet and water until 180 days old (1 animal from each litter, n=7). Significant differences had p<0.05. The SL group presented higher adrenal catecholamine content (absolute: +35% and relative: +40%), tyrosine hydroxylase (+31%), DOPA decarboxylase (+90%) protein contents, basal and caffeine-induced catecholamine in vitro secretion (+35% and +43%, respectively). However, hormones of the hypothalamic-pituitary-adrenal cortex axis were unchanged. The β3-adrenergic receptor content in visceral adipose tissue was unchanged in SL rats, but the β2-adrenergic receptor in the liver was lower (-45%). SL group showed higher glycogen and triglycerides contents in liver (+79% and +49%, respectively), which showed microesteatosis. Although the neonatal overfeeding leads to higher adrenomedullary function, adult obese SL rats have a dysfunction in hepatic β2-adrenergic receptor, which can contribute for the hepatic dysfunction characteristic of liver obesity complications.