Assessment of hypothalamic inflammation and the blood-brain barrier in an experimental colitis model associated with high-fat diet consumption

• Grant number: 24/22958-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcio Alberto Torsoni
• Grantee: Catarina Michelone
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, have high prevalence and morbidity in the population. These pathologies have a multifactorial etiology, but emotional and nutritional aspects are directly related to disease progression. Common inflammatory indicators in IBDs include the presence of pro-inflammatory cytokines and increased intestinal permeability, which allows the infiltration of molecules such as lipopolysaccharides. In this context, previous studies from the group indicate that a high-fat diet (HFD) enhances the inflammatory response by reducing the expression of the alpha7 nicotinic cholinergic receptor (¿7nAChR), a receptor with anti-inflammatory properties. Furthermore, the connection between the gut, the central nervous system (CNS), and the intestinal microbiota, known as the microbiota-gut-brain axis, is discussed, as well as its associations with damage to the blood-brain barrier (BBB). Just like in the gut, such damage to the BBB is associated with the presence of pro-inflammatory cytokines and increased permeability. Thus, it is believed that changes in the microbiota and intestinal inflammation, together with the harmful effects of HFD, can promote inflammation and affect BBB permeability. This may be linked to alterations in hypothalamic function. In this sense, the study proposes to investigate the effects of the association between HFD consumption and experimental colitis on permeability and inflammation in the hypothalamus of mice. C57BL/6 wild-type male mice aged 6 weeks will be used, divided into a control group, a group with colitis that will receive a control diet, and a group with colitis that will receive an HFD (45%) for 4 weeks. Afterward, the animals will be used to assess permeability, and the hypothalami will be collected for Western blotting and qPCR analyses. Proteins and genes related to cell junctions and inflammation will be evaluated.