Effects of maternal nutrition in fetal and neonatal periods on sexual dimorphism and monocyte chemotaxis in high-fat diet-induced hypothalamic inflammation.

• Grant number: 23/09032-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Natália Ferreira Mendes
• Grantee: Nicolly Porto Marin
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 22/06282-7 - Involvement of CXCL12/CXCR4 pathway in monocyte chemotaxis and postnatal neurogenesis during hypothalamic inflammation and of maternal obesity in monocyte sexual dimorphism., AP.GR

Abstract

In obesity, there is a chronic low-grade inflammatory state that involves the chemotaxis of immune cells to various tissues. In mice, a few days after the introduction of a high-fat diet (HFD) an inflammatory response is observed in the hypothalamus. The chemotaxis of monocytes in this region, however, is observed after a few weeks in the chronic phase of inflammation. Through bioinformatic analysis of the transcriptome of CCR2+ monocytes isolated from the hypothalamus of HFD-fed mice, thousands of differentially expressed genes involved in the chemotaxis process were found, with important sexual dimorphism. It is still not known in which period of development this dimorphism originates, nor if it is modulated by maternal nutrition. In this project, we will evaluate whether maternal obesity in fetal and neonatal life modifies the transcriptome of CCR2+ monocytes in the offspring and the serum profile of chemokines and markers related to chemotaxis in these animals. Through an observational clinical study, we will also evaluate whether maternal obesity modifies the serum profile of chemokines and chemotaxis-related markers in newborns. The proposed translational approach will contribute to obtaining novel data on the effects of maternal nutrition on the CCR2+ monocyte transcriptome, and to advance the characterization of biomarkers that predispose to the development of infectious and inflammatory diseases, such as obesity and its comorbidities, from early life.