Effects of maternal protein restriction on metabolic parameters and oxidative stress in liver profile of old male rats: a DOHaD approach

• Grant number: 23/13012-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): April 01, 2024
• Effective date (End): March 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Luis Antonio Justulin Junior
• Grantee: Pedro Menchini Vitali
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Adverse conditions during pregnancy and/or early childhood can lead to morphophysiological changes in the offspring, a condition associated with Developmental Origins of Health and Disease (DOHaD). Maternal protein restriction (MPR) is one of the models used for studies on this concept, and experimental studies elucidate that this condition is associated with metabolic, cardiovascular and renal diseases, affects reproductive parameters and increases the incidence of some types of cancer. In this context, it has been demonstrated that the liver, the central organ of metabolism and detoxification, is also affected by exposure to MPR, and the impacts in the gestational period and early life can potentiate the effects during aging. Thus, the aim of this project is to evaluate if MPR affects the hepatic morphophysiology of aging rats, with a focus on inflammatory parameters. For this, Sprague Dawley rats were divided into two experimental groups: 1- Control (CTR): Rats born from mothers who consumed normal protein chow (17% protein) and water ad libitum during pregnancy and lactation; 2- Maternal protein restriction (GLLP): Rats born from mothers who consumed hypoproteic chow (6% protein) during pregnancy and lactation and who, after weaning, consumed normoproteic chow and water ad libitum until the postnatal day (PND) 540, when they were anesthetized, weighed, euthanized and the liver was collected. These samples were processed and will be used for morphological, morphometric and immunohistochemical analyzes for marking immune system cells (CD4, CD8 and CD68), in addition to protein expression, by western blotting, for pro-inflammatory factors (TNF± and IL6 ) and anti-inflammatory drugs (TGFß1 and IL10). Thus, the expected results are that MPR modulates hepatic morphophysiology from the gestational period, creating a window of susceptibility to metabolic disorders with development, leading to an imbalance in hepatic inflammatory parameters with aging.