The influence of obesity on the MFSD2A receptor expression and function in the hypothalamus

• Grant number: 23/12208-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2024
• End date: January 31, 2025
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Dennys Esper Corrêa Cintra
• Grantee: Camila Venturini Ayres Cunha
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

Nutritional status is a key determinant of central nervous system (CNS) development. Most studies point to the deleterious impact of malnutrition, however, the impact of overnutrition is also a warning. The low-grade inflammatory process associated with obesity can alter the overall permeability of organic biological barriers, among them the blood-brain barrier (BBB). Inflammation inducing changes in junction proteins and configuring loss of selectivity is well known, however, there also seems to be an influence of inflammation on the biological response pattern responsible for the translocation of essential fatty acids to the CNS. The present project focuses on the MFSD2A (major facilitator superfamily domain containing 2A) protein, present in the BBB, which has high specificity for the translocation of É3 fatty acid from the periphery to the CNS. Data from our laboratory point to the reduced concentration of omega-3 in the brain of mice and the cerebrospinal fluid of obese humans. Thus, this project aims to evaluate whether obesity can impact the gene expression, protein content, and translocator function of MFSD2A protein in the brain of mice submitted to the obesogenic process. For this, mice will be submitted to a high saturated fat diet and after the onset of obesity, the neuronal groups present in the BBB, near the middle eminence of the hypothalamus, will be examined for their function in the uptake of É3, together with the MFSD2A protein. The hypothesis is that, in the context of obesity, there is a reduced presence and function of this protein, but not necessarily from the inflammatory process, since saturated fat itself could control the expression of the MFSD2A gene. If the hypothesis is confirmed, it will be an impactful finding on mental/nutritional health, since obesity is a pandemic, and É3 fatty acid is essential for the formation and functioning of the CNS.