Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/242416
Type: Artigo
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-T(H)2 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 KDHOM-/-), 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.
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-T(H)2 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 KDHOM-/-), 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: Ativação enzimática
Camundongos obesos
Fosforilação
Country: Estados Unidos
Editor: Elsevier
Citation: Increased Airway Reactivity And Hyperinsulinemia In Obese Mice Are Linked By Erk Signaling In Brain Stem Cholinergic Neurons. Cell Press, v. 11, p. 934-943 MAY-2015.
Rights: aberto
Identifier DOI: 10.1016/j.celrep.2015.04.012
Address: https://www.sciencedirect.com/science/article/pii/S2211124715003873?via%3Dihub
Date Issue: 2015
Appears in Collections:FCM - Artigos e Outros Documentos

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