Effects of acute exposure to high-fat diet on epigenetic control that may modulate ±7nAchR receptor expression in hypothalamic cells.

• Grant number: 23/11551-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2023
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcio Alberto Torsoni
• Grantee: Melissa Santos de Aguiar
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated scholarship(s): 24/21772-6 - The role of the a7nAChR receptor in preventing the activation of the ceramide pathway, BE.EP.IC

Abstract

The hypothalamus is one of the main regulatory centers of energy homeostasis and metabolic disorders such as obesity are related to hypothalamic signaling damage. In this sense, the alpha 7 subunit of the nicotinic cholinergic receptor (±7nAChR) expressed in hypothalamic neurons seems to modulate the expression of neuropeptides that favor negative energy balance, such as pro-opiomelanocortin (POMC). The expression and activity of the ±7nAChR receptor depends on several cellular controls that can act by stimulating or inhibiting the expression of the Chrna7 gene or even by controlling the presence and activity of the receptor on the membrane, such as methylation and chaperone proteins. Thus, the present study intends to investigate the effects of acute exposure to a high-fat diet on the epigenetic control related to the ±7nAchR receptor in hypothalamic cells. Therefore, male mice will be used, in the 8th week of life, which will be divided into two experimental groups: control animals and animals with dietary intervention, which will be exposed to a high-fat and high-calorie diet for 3 days (DHH; 45% kcal/lipid ). At the end of the dietary manipulation, the animals will be fasted for 24 hours and euthanized, with the serum and hypothalamus being extracted. The serum will be used for the treatment of mHypoA-POMC/GFP cells and then the inflammatory effect on pre-transcriptional and/or post-translational switches of ±7nAchR expression will be evaluated. Both the hypothalamus and the cells treated with serum will be evaluated for gene expression of: neuropeptides (Pomc, Cart, NPY and AgRP), ±7nAchR, chaperones (RIC3 and NACHO) and DNA-methyltransferases (DNMT) by RT-qPCR.