Evaluation of the extracellular matrix and its components as mediators of hypothalamic inflammation in obesity.

• Grant number: 24/18774-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Natália Ferreira Mendes
• Grantee: Giovanna Ariozi dos Santos
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Excessive intake of saturated fats induces an inflammatory response in the hypothalamus, involving interactions between parenchymal cells and infiltrating myeloid cells. Prolonged exposure to this dietary pattern leads to hypothalamic dysfunction, characterized by impaired neuronal regulation of energy balance, which contributes to the onset of obesity. The extracellular matrix (ECM) is essential for maintaining the structural integrity and homeostasis of neural tissue. Composed of proteins, glycoproteins, polysaccharides, and other molecules, the ECM forms a complex network surrounding cells, providing both structural and biochemical support. During inflammation, the ECM undergoes dynamic remodeling and interacts with immune cells, mediating processes such as chemotaxis, activation, proliferation, and differentiation within inflamed tissue. Although significant advances have been made in understanding the role of different cell types in hypothalamic inflammation, the specific involvement of ECM components in this process remains largely unexplored. The objective of this study is to assess the gene expression of ECM components in the hypothalamus of adult male and female C57BL/6J mice subjected to a high-fat diet for both short (1 and 3 days) and long (14 and 28 days) durations. We will also investigate whether alterations in estrogen levels, induced by bilateral ovariectomy in female mice, influence the expression of ECM components, given the well-established role of reduced estrogen in promoting obesity. This research will provide novel insights into the regulation of ECM components by dietary factors and ovarian hormones, offering new perspectives on potential therapeutic targets for the treatment and prevention of obesity.