Maternal protein restriction associated with post-weaning sugar consumption in offspring: Effects on the proteomic profile in the liver of young and senile rats

Abstract

Adverse gestational conditions can cause irreversible morphofunctional changes in the offspring, a condition derived as Developmental Origin of Health and Disease (DOHaD). Perinatal protein restriction (PPR), a model used for studies on DOHaD, has been associated with an increased incidence of cardiovascular and renal diseases, in addition to affecting reproductive parameters and the development of some types of cancer. In addition, postnatal exposure to hypercaloric/hyper lipidic diets can amplify the damage caused by PPR, increasing to aggravate diseases with aging. In this context, it has been characterized that the liver, a central organ with metabolism control and detoxification, is also affected by exposure to obesogenic diets early in life. Our research group shows that PPR impacts the metabolic offspring parameters, in addition to increasing the incidence of prostatic lesions in old animals. Thus, this project aims to identify the global protein profile expression in the liver of rats submitted to PPR (gestational and lactational) and exposed to postnatal sugar consumption. The rats will be divided into the following experimental groups: 1- Control (CTR): Rats born to dams who will consume normal diet (17% protein) and water ad libitum during pregnancy and lactation; 2-Control + sugar (CTR+SUG): The same treatment as CTR and which will consume sugar solution (10% diluted in water) from the postnatal day (PND) 21 until PND 90; 3- Perinatal protein restriction (RPP): Rats born to dams who will consume hypoproteic diet (6% protein) during pregnancy and lactation and who will later consume normal diet and water ad libitum until PND 90; 4- PPR+SUG Group: rats born to dams fed with hypoprotein diet during pregnancy and lactation and that will consume normal diet and sugar solution (10% diluted in water) ad libitum from the PND 21 until PND 90. In PND 90 and 540 the animals will be anesthetized, weighed, euthanized and the liver will be collected. These will be submitted to a proteomic analysis by mass spectrometry (LC-Ms/Ms), morphological and morphometric analyzes, oxidative stress analysis and metabolic analyzes will also be done. After that, perform integrative and comparative analysis of these data between the experimental groups, in addition to in silico analyzes, comparing our results with other experimental models and with patient data. Some targets will be selected for validation in western blotting, immunohistochemistry and RT-qPCR. Thus, it is expected to obtain an overview of the effects of fetal programming by perinatal protein restriction on the liver of the offspring.