Effects of maternal low protein diet associated with high glucose intake by the offspring on liver morphology, fibrosis and cellular proliferation from male rats

Abstract

Perinatal protein restriction (RPP) has been associated with an increase in the incidence of cardiovascular and renal diseases, besides affecting reproductive parameters and the development of some types of cancer. In addition, exposure of these individuals to a second insult in postnatal life may amplify the damage caused by RPP by increasing the incidence of these diseases with aging. Our group demonstrated that RPP impacts development and increases the incidence of prostatic lesions in the offspring of old rats. In this project, taking advantage of other organs of our experiments, we will evaluate the liver of RPP animals against postnatal exposure to the consumption of refined sugar (most consumed form of sugar) when compared to rats born of normal gestation. More specifically, we will investigate whether the maternal protein restriction followed by sugar consumption alters the morphology, fibrosis, proliferation and incidence of liver damage in rats (90 days old) and aged (540 days). Sprague-Dawley rats will be divided into the following experimental groups: 1- Control (RTC): Rats born to mothers who will consume normal ration (17% protein) and water ad libitum during gestation and lactation; 2-Control + sugar (CTR + ACU): The same treatment of CTR and that will consume sugar solution (10% diluted in water) from the postnatal day (PND) 21 until the end of the experiment; Perinatal protein restriction (RPP): Rats born to mothers who will consume a hypoprotein diet (6% protein) during gestation and lactation and who will later consume normal ration and water ad libitum until the end of the experiment; 4 - RPP + ACU group: rats born from mothers fed with hypoprotein ration during gestation and lactation and who will consume normal ration and sugar solution (10% diluted in water) ad libitum from postnatal day 21 until the end of experiment. In TDPs 90 and 540 animals will be anesthetized, weighed, euthanized and the liver will be collected for histopathological analysis, collagen deposition as well as immunohistochemistry for Ki-67. It is expected to contribute to the understanding of the effects of fetal programming by protein restriction followed by sugar consumption on liver morphophysiology and repercussions on the incidence of lesions with aging.