Role of alpha7 nicotinic acetylcholine receptor (alpha7nAChR) in preventing insulin resistance in hypothalamic cells.

• Grant number: 16/23833-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2017
• End date: August 31, 2021
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcio Alberto Torsoni
• Grantee: Camila Libardi Do Amaral
• 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

Abstract

Insulin resistance is defined as a state of decreased tissue responsiveness to normal circulating levels of insulin and one of its main determinants is the chronic inflammation induced by obesity. Considering that world's prevalence of obesity and diabetes mellitus type 2 is raising continuously, it is extremely important to investigate new targets capable of overcome insulin resistance, so that new alternative therapies can be developed. Thus, this project aims to the study an anti-inflammatory mechanism still poorly investigated in insulin resistance: the cholinergic anti-inflammatory pathway, a neural mechanism that controls inflammation, which is dependent on the activation of the ±7 nicotinic acetylcholine receptor (±7nAChR). Obese individuals have decreased expression of this receptor and treatment with ±7nAChR agonists improves peripheral insulin sensitivity in obese mice. However, despite being widely expressed among cells of the nervous system, the effect of ±7nAChR activation on the metabolic and cognitive dysfunctions induced by hypothalamic insulin resistance have not yet been investigated. Thus, this project intends to evaluate the effect of ±7nAChR activation in reducing hypothalamic insulin resistance in response to inflammatory pathways and investigate the associated mechanism, using neuronal and microglial cell lines and mice (Swiss) fed with high fat diet.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DO AMARAL, CAMILA LIBARDI; ALVES MARTINS, ISIS DE CASSIA; COSTA VERAS, ALANA CAROLINA; SIMABUCO, FERNANDO MOREIRA; ROSS, MICHAEL GLENN; DESAI, MINA; IGNACIO-SOUZA, LETICIA MARTINS; MILANSKI, MARCIANE; TORSONI, ADRIANA SOUZA; TORSONI, MARCIO ALBERTO. Activation of the alpha 7 Nicotinic Acetylcholine Receptor Prevents against Microglial-Induced Inflammation and Insulin Resistance in Hypothalamic Neuronal Cells. CELLS, v. 11, n. 14, p. 15-pg., 2022-07-01. (16/23833-6, 19/07615-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

AMARAL, Camila Libardi Do. Role of alpha7 nicotinic acetylcholine receptor (alpha7nAchR) in preventing insulin resistance in hypothalamic cells. 2022. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas Limeira, SP.