Long-term metabolic consequences of diet-induced fetal programming in CCR2-knockout mice

• Grant number: 25/11437-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Natália Ferreira Mendes
• Grantee: Lucas Dantzger
• 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

Circulating myeloid cells infiltrate the hypothalamus of mice fed a high-fat diet (HFD), where they interact with resident neural tissue cells, impacting energy balance and glucose metabolism. In a recent study, we identified a significant sexual dimorphism in the transcriptome of CCR2-positive cells that infiltrate the hypothalamus in this context, which may partially explain the distinct metabolic responses between males and females when fed on a HFD. It is still unclear at what stage of development this transcriptional difference is established, but it is plausible that it originates during the gestational period, given that these cells derive from hematopoietic progenitors, initially differentiating in the fetal liver and later migrating to the bone marrow - the main site of monocyte production and reservoir during postnatal life. To date, no studies have evaluated how fetal metabolic programming induced by a HFD impacts energy balance in adulthood in the absence of the CCR2 receptor, a molecule fundamental for monocyte migration from bone marrow to peripheral tissues. Therefore, this study proposes to investigate whether maternal exposure to HFD before and during gestation, as well as during lactation, promotes long-term metabolic alterations in CCR2-knockout mice. This project will offer new perspectives on the effects of maternal nutrition on long-term metabolic programming in offspring, with emphasis on the role of CCR2-positive immune cells in these changes.