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Type: Artigo de periódico
Title: Increased Airway Reactivity And Hyperinsulinemia In Obese Mice Are Linked By Erk Signaling In Brain Stem Cholinergic Neurons.
Author: Leiria, Luiz O S
Arantes-Costa, Fernanda M
Calixto, Marina C
Alexandre, Eduardo C
Moura, Rodrigo F
Folli, Franco
Prado, Carla M
Prado, Marco Antonio
Prado, Vania F
Velloso, Licio A
Donato, José
Antunes, Edson
Martins, Milton A
Saad, Mario J A
Abstract: Obesity is a major risk factor for asthma, which is characterized by airway hyperreactivity (AHR). In obesity-associated asthma, AHR may be regulated by non-TH2 mechanisms. We hypothesized that airway reactivity is regulated by insulin in the CNS, and that the high levels of insulin associated with obesity contribute to AHR. We found that intracerebroventricular (ICV)-injected insulin increases airway reactivity in wild-type, but not in vesicle acetylcholine transporter knockdown (VAChT KD(HOM-/-)), mice. Either neutralization of central insulin or inhibition of extracellular signal-regulated kinases (ERK) normalized airway reactivity in hyperinsulinemic obese mice. These effects were mediated by insulin in cholinergic nerves located at the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (NA), which convey parasympathetic outflow to the lungs. We propose that increased insulin-induced activation of ERK in parasympathetic pre-ganglionic nerves contributes to AHR in obese mice, suggesting a drug-treatable link between obesity and asthma.
Subject: Animals
Brain Stem
Bronchial Hyperreactivity
Cholinergic Neurons
Diet, High-fat
Enzyme Activation
Extracellular Signal-regulated Map Kinases
Injections, Intraventricular
Map Kinase Signaling System
Methacholine Chloride
Mice, Inbred C57bl
Mice, Obese
Phosphatidylinositol 3-kinases
Receptor, Insulin
Citation: Cell Reports. v. 11, n. 6, p. 934-943, 2015-May.
Rights: aberto
Identifier DOI: 10.1016/j.celrep.2015.04.012
Date Issue: 2015
Appears in Collections:Unicamp - Artigos e Outros Documentos

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