Characterization of hypothalamic vascular remodeling induced by a high-fat diet

• Grant number: 25/12765-9
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: October 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Natália Ferreira Mendes
• Grantee: Natália Ferreira Mendes
• Principal researcher abroad: Caroline Menard
• Institution abroad: Université Laval, Canada
• 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

A high-fat diet (HFD) induces inflammation in the hypothalamus, a brain region essential for the control of energy homeostasis. This response includes vascular changes such as blood-brain barrier (BBB) breakdown, endothelial dysfunction, and angiogenesis. The median eminence (ME), a circumventricular organ (CVO) that relays metabolic signals to the arcuate nucleus (ARC), is also affected. Located at the base of the hypothalamus, the ME contains fenestrated capillaries that lack BBB protection and serves as an interface between the brain and peripheral endocrine systems. These vascular and anatomical features make the ARC and ME especially vulnerable to harmful substances and infiltration by peripheral immune cells. CXCL12, also known as SDF1-alpha, is a chemokine predominantly expressed by endothelial cells of blood capillaries in the ARC/ME. In inflamed tissues, CXCL12 plays a dual role by recruiting immune cells and promoting angiogenesis. However, its role in hypothalamic vascular remodeling under HFD-induced inflammation remains unexplored. In the first phase of this project, we aim to investigate whether an HFD modulates endothelial CXCL12 expression in ARC/ME capillaries, and whether this chemokine contributes to the vascular remodeling observed during diet-induced hypothalamic inflammation. The initial phase of this collaborative proposal includes a mission in CERVO Brain Research Center (Quebec, Canada) during which Dr. Mendes will obtain high-resolution images of CXCL12 production and release by endothelial cells from the ARC/ME of mice fed an HFD, building on Dr. Caroline Menard's expertise in advanced imaging techniques targeting brain vasculature. This collaboration will open the door to future joint research proposals and build a long-term partnership between the two teams. (AU)