Programmed molecular mechanisms in insulin sensitivity associated with changes in expression of miRNAs in adipocytes from male and female offspring by maternal diet-induced obesity

• Grant number: 22/05377-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): November 20, 2022
• Effective date (End): August 24, 2023
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Luciana Pellegrini Pisani
• Grantee: Marcela Nascimento Sertorio
• Supervisor: Susan Ozanne
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Research place: University of Cambridge, England
• Associated to the scholarship: 18/17412-3 - Effects of maternal and paternal intake of high fat and high sugar diet on male reproductive programming of offspring in early adulthood, BP.DR

Abstract

Maternal obesity prior to or during gestation and/or lactation leads to developmental programming resulting in obesity-related metabolic disorders in adult offspring, such as insulin sensitivity. The relationship between the maternal environment and the offspring phenotype during life has been investigated through an epigenetic approach and microRNAs (miRNAs) have been identified as key players in the scenario. In a previous study carried out at the University of Cambridge in partnership with UNIFESP, the full spectrum of adipose tissue miRNAs programmed as a consequence of maternal obesity was established through small RNA sequencing of isolated adipocytes using a mouse model of maternal diet-induced obesity. Some of the programmed changes displayed sexual dimorphism. The current project builds on these findings and aims to determine which among the candidate miRNAs are programmed cell autonomously and to establish which ones may be involved mechanistically in mediating programmed changes in insulin sensitivity. Programmed miRNAs in the adipocytes will be validated by qPCR and their potential targets confirmed through Western blotting and luciferase assay. This will allow us to define the miRNAs with the strongest potential to influence insulin sensitivity pathways via their putative target genes. Functional consequences of dysregulation of the programmed miRNAs will be determined through over-expression of miR mimic/antago-miRs in adipocyte cell lines. The results from this study will provide a better understanding of the mechanisms involved the programming of insulin sensitivity by maternal obesity and identify new putative targets for related disease therapy, some of which may be sex-specific. (AU)