Evaluation of modulation of hypothalamic BDNF expression under acute high-fat diet exposition

• Grant number: 22/12938-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2022
• Effective date (End): September 30, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Licio Augusto Velloso
• Grantee: Louise Buonalumi Tácito Yugar
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Obesity is a chronic non-communicable disease associated with many complications, such as type 2 diabetes mellitus, cardiovascular diseases, increased mortality, among several others. It depends on a positive energy balance, caused by excessive ingestion of calories as in high-fat diets. Energy homeostasis is the balance between caloric ingestion and energy expenditure, and it is controlled primarily by the arcuate nucleus in the hypothalamus, where the anorexigenic POMC neurons and the orexigenic AgRP neurons are localized. In obesity, the hypothalamus is affected by neuroinflammation, which involves the microglia and can result in apoptosis, worsening the energy imbalance. BDNF is a neurotrophic factor involved in neurogenesis, energy homeostasis, and the pathophysiology of obesity. Single-cell RNAseq analyses of different cell populations in the hypothalamus and their transcripts identified two hypothalamic subpopulations capable of producing BDNF: FezF1 and Kiss1. The FezF1 neurons are poorly characterized, and the Kiss1 neurons are related to reproduction and have connections to the neurons in the arcuate nucleus. There is evidence of BDNF production by the microglia, a process involved in neuropathic pain and cognitive functions. Recently, it was also associated with weight loss in mice. Therefore, this project aims to evaluate the modulation of BDNF expression in these cell populations in animals with acute exposition to a high-fat diet.