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Title: Increased Airway Reactivity and Hyperinsulinemia in Obese Mice Are Linked by ERK Signaling in Brain Stem Cholinergic Neurons
Authors: Leiria, Luiz O. S.
Arantes-Costa, Fernanda M.
Calixto, Marina C.
Alexandre, Eduardo C.
Moura, Rodrigo F.
Folli, Franco
Prado, Carla Máximo [UNIFESP]
Prado, Marco Antonio
Prado, Vania F.
Velloso, Licio A.
Donato, Jose
Antunes, Edson
Martins, Milton A.
Saad, Mario J. A.
Universidade Estadual de Campinas (UNICAMP)
Universidade de São Paulo (USP)
Univ Texas Hlth Sci Ctr San Antonio
Universidade Federal de São Paulo (UNIFESP)
Univ Western Ontario
Issue Date: 12-May-2015
Publisher: Cell Press
Citation: Cell Reports. Cambridge: Cell Press, v. 11, n. 6, p. 934-943, 2015.
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.
ISSN: 2211-1247
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