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

Author(s)

Isabelle Tenori Ribeiro

• Document type: Master's Dissertation
• Press: Botucatu. 2023-04-19.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2023-02-24
• Advisor: Sérgio Alexandre Alcantara dos Santos; Luis Antonio Justulin Junior

Abstract

Adverse gestational conditions can cause irreversible morphofunctional changes in the offspring, a condition derived as Developmental Origin of Health and Disease (DOHaD). Maternal protein restriction (MPR), 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 MPR, 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 MPR impacts the metabolic offspring parameters in early life and aging. Thus, this project aims to identify the impact of maternal protein restriction on the liver of young and old rats, associated with postnatal sugar consumption. The rats were separated into the following experimental groups: 1- Control (CTR): Rats born to dams who consumed normal diet (17% protein) and water ad libitum during pregnancy and lactation; 2-Control + sugar (CTR+SUG): The same treatment as CTR and which consumed sugar solution (10% diluted in water) from the postnatal day (PND) 21 until PND 90; 3- Gestational and lactational low protein diet (GLLP): Rats born to dams who consumed hypoproteic diet (6% protein) during pregnancy and lactation and who consumed normal diet and water ad libitum until PND 90; 4- Gestational and lactational low protein diet + sugar (GLLP+SUG): rats born to dams fed with hypoprotein diet during pregnancy and lactation and that consumed normal diet and sugar solution (10% diluted in water) ad libitum from the PND 21 until PND 90. In DPN 90 and 540 the animals were anesthetized, weighed, euthanized and the livers were collected. Biometric and nutritional analyses, oral glucose tolerance test (OGTT), morphological and morphometric analyses, oxidative stress analysis, metabolic analyses, liver glycogen analysis, immunohistochemistry, Western Blotting and proteomics were performed. After that, integrative and comparative analysis of these data between the experimental groups were carried out. The results obtained demonstrate changes in biometric and nutritional parameters, changes in antioxidant enzymes. In addition, proteomics indicated alterations in the metabolism of these animals, both in DPN 90 and in DPN 540. In immunohistochemistry, we observed the presence of significant immunostaining in the RPGL and RPGL+AÇU groups. The results indicate that RPM resulted in lower offspring weight, liver morphophysiological changes and direct effects on enzymatic activities and liver metabolism, both in DPN 90 and DPN540. When RPM is associated with sugar consumption, it alters glucose levels, causing glucose intolerance and possibly insulin sensitivity. Therefore, the results demonstrate that RPM associated with postnatal sugar intake modulates proteins and important metabolic pathways in the liver of adult and old animals, which may have negative consequences not only on the hepatic tissue, but also on the systemic environment. (AU)

• FAPESP's process: 21/01952-1 - Maternal protein restriction associated with post-weaning sugar consumption in offspring: Effects on the proteomic profile in the liver of young and senile rats
• Grantee: Isabelle Tenori Ribeiro
• Support Opportunities: Scholarships in Brazil - Master