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

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.