Role of alpha7nAChR cholinergic receptors in hypothalamic POMC neurons on the control of energy homeostasis in mice

• Grant number: 20/06661-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2020
• Effective date (End): August 31, 2024
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Marcio Alberto Torsoni
• Grantee: Wenicios Ferreira Chaves
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated research grant: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID
• Associated scholarship(s): 23/02027-5 - Mapping of the alpha 7 nicotinic acetylcholine receptor subunit expression in different brain areas during different ages and after chronic exposure to a high-fat diet, BE.EP.DR

Abstract

The cholinergic system is widely expressed in the body, highlighting the role of alpha7nAChR receptor in the systemic anti-inflammatory response. However, recent studies have shown that the nicotinic receptor, expressed in hypothalamic neurons, contributes to the maintenance of energy homeostasis. In this sense, the aim of this study will be to evaluate the role of the alpha7nAChR receptor in hypothalamic POMC neurons on food intake, liver metabolism and energy homeostasis in mice. In this study, we will generated mice with deletion of the alpha7nAChR and the STAT3 in POMC neurons obtained through the Cre-LoxP protocol. In addition, a part of the animals obtained will be submitted to high-fat diet protocol (4.6 kcal/g; 45% kcal/lipids) for 8 weeks. Body weight and food intake will be accompanied by weaning until 8th week of life, weekly. In the 4th and 8th weeks, the peripheral response to insulin and glucose will be determined through insulin and glucose tolerance tests. At these ages, the indirect calorimetry system will also be used to measure energy expenditure, mobility and other metabolic parameters. While in the 7th week, some animals will undergo stereotaxic surgery to implant the cannula. The animals will receive single administrations of leptin or PNU-282987 and will subsequently be euthanized. The hypothalamus, liver and white and brown adipose tissues will be extracted for PCR and Western blotting analyzes to POMC, alphaMSH, AgRP and NPY, pSTAT3, pAkt, PEPCK, G6Pase, UCP- 1 and pHSL. Animals submitted to a high-fat diet will have the leptin signaling pathway in the hypothalamus analyzed. (AU)