Effects of maternal nutritional supplementation with a leucine-rich diet on the modulation of cancer effects on biochemical, molecular, and omics parameters in the cardiac tissue of adult offspring, in in vitro and in vivo assays.

• Grant number: 24/07207-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2025
• End date: June 30, 2029
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Maria Cristina Cintra Gomes Marcondes
• Grantee: Ninón Melany Flores Barrios
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Cancer-related to pregnancy is becoming more prevalent due to demographic changes such as advanced maternal age. Cachexia, characterized by muscle mass loss, is common in patients with advanced cancer, with cardiac cachexia being one of the most severe forms, associated with heart failure and significant mortality. Nutrition plays a crucial role in cancer treatment, and leucine has been studied for its ability to combat muscle degradation, influence tumor metabolism, and improve mitochondrial function in cancer patients. Previous studies suggest that maternal supplementation with leucine may have benefical effects in reducing cachexia in adult offspring, affecting protein turnover and metabolic profiles. This study aims to investigate the impact of a leucine-rich diet on preventing the effects of tumor growth on the cardiac tissue of pregnant Wistar rats and their adult offspring, both females and males. The study seeks to understand the epigenetic effects of leucine supplementation on gene expression and cardiac health of adult descendants by comparing sexes. Transcriptomic and DNA methylation analyses will be conducted on in vivo cardiac tissue, along with in vitro genetic manipulations in H9c2 cardiac cells, to elucidate the underlying mechanisms of leucine modulation in this context. This study aims to fill gaps in understanding the metabolic and epigenetic mechanisms associated with cancer cachexia, highlighting the potential of leucine as a promising adjunct therapy during pregnancy to improve the quality of offspring. (AU)