Effects of maternal nutrition in fetal and neonatal periods on monocyte chemotaxis in high-fat diet-induced hypothalamic inflammation in adult life

• Grant number: 23/04860-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2023
• End date: December 31, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Licio Augusto Velloso
• Grantee: Igor Vinicius Sousa Cavalheiro
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

The prevalence of obesity has been increasing worldwide, reaching all age groups, including women of reproductive age. 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 of a high-fat diet (HFD) triggers an inflammatory response in the hypothalamus, the main regulatory center of energy homeostasis. After a few weeks, when the hypothalamic inflammation is already established, monocyte chemotaxis and reduction in postnatal neurogenesis are observed, with suppressed turnover of neurons involved in energy balance. Bioinformatic analysis of the transcriptome of CCR2+ monocytes isolated from the hypothalamus of HFD-fed mice shows thousands of differentially expressed genes involved in the chemotaxis, with an important sexual dimorphism. To date, it is unknown in which period of life the sexual dimorphism of the CCR2+ monocytes transcriptome is originated, nor if this is modulated by maternal obesity. Here we will evaluate whether maternal obesity during gestation and neonatal life modifies the susceptible to monocyte chemotaxis in the hypothalamus in offspring when exposed to HFD in adulthood. These data will promote an advance in the identification of new biomarkers that predispose the development of inflammatory diseases, such as obesity and its comorbidities, from the beginning of life