Hormonal, nutritional and inflammatory factors and microRNAs modulation related to the altered cholinergic anti-inflammatory response in Obesity

• Grant number: 20/07257-0
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): August 01, 2020
• Effective date (End): July 31, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal researcher: Marcio Alberto Torsoni
• Grantee: Laís Angélica de Paula Simino
• Home 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

The imbalance between the calories ingested and the energy expended is the fundamental cause of Obesity, and the regulation of this energy balance is mainly performed by the hypothalamic arcuate nucleus (ARC) and its populations of orexigenic and anorectic neurons. Nicotinic cholinergic receptors play an important role in the functional regulation of these hypothalamic neurons, since they alter neuronal excitability, favoring the secretion of neurotransmitters. The a7 nicotinic acetylcholine receptor (a7nAChR), when activated by acetylcholine, culminates in the inhibition of inflammatory cytokine production. In addition, recent studies have correlated the modulation of this receptor with the development of hyperphagia and Obesity, since the consumption of a high-fat diet leads to a decrease in a7nAchR expression, while its activation leads to changes in the response to food intake. However, the mechanisms by which a7nAChR receptors are differentially expressed in Obesity or obesogenic diet consumption are not yet known, but the modulation of epigenetic factors may play an important role in this phenomenon. Thus, our hypothesis is that hormonal, nutritional and inflammatory factors that permeate the genesis of Obesity, can be related to modification in epigenetic mechanisms, such as microRNAs expression, that may alter a7nAChR receptor expression and activation in ARC, modulating the expression of neuropeptides that regulate energy homeostasis and contributing to the development of Obesity and related metabolic diseases. (AU)