Effect of intracerebroventricular administration of irisin on hippocampal inflammation in obese C57BL/6Unib mice

• Grant number: 24/04870-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2024
• Effective date (End): May 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Helena Cristina de Lima Barbosa
• Grantee: Júlia Cerqueira Santos
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/04664-7 - Molecular mechanisms involved in pancreatic beta cell dysfunction and death in Diabetes Mellitus: strategies for the inhibition of these processes and restoration of the insular mass, AP.TEM

Abstract

Obesity is a multifactorial disease and a significant risk factor for the development of neurodegenerative disorders. One of the main factors involved in the genesis of this pathology is the high consumption of ultra-processed foods, which is associated with a sedentary lifestyle. A diet based on this type of food has a high fat content, which is associated with a condition of systemic low-grade chronic inflammation, affecting brain areas such as the hippocampus. Pathologies in this region involve neurodegeneration, which can lead to diseases such as Parkinson's, Alzheimer's, and multiple sclerosis, in addition to a high risk of developing psychosocial disorders. Thus, aiming at a potential target for combating obesity and associated complications, irisin has gained significant scientific focus in recent years. It has already been demonstrated that intraperitoneal administration of this myokine promotes the reduction of hippocampal inflammation by decreasing the activation of the p38 protein. However, data on the effects of direct administration in the central nervous system are scarce, and there is still no evidence of this methodology's use in obese animals. Therefore, aiming to evaluate irisin's anti-inflammatory effect in the hippocampus, this study focuses on obese C57BL/6 mice fed a high-fat diet for 13 weeks and treated with irisin for 7 days. Samples from the mice's hippocampi will be collected for evaluation of the gene content of BDNF, FNDC5, DCX, and NCAM, as well as inflammatory markers (TLR4, TNF±, IL-1², IL-6, and INFg), anti-inflammatory markers (IL-10 and IL4), and cell death markers (BAX and BCL-2); additionally, central sensitivity to leptin will be assessed through the evaluation of pSTAT3 protein content after ICV injection of the hormone. The outcomes of this project are expected to significantly enhance understanding of irisin's central actions and inform therapies for cognitive complications linked to metabolic dysfunctions.