PT  - JOURNAL ARTICLE
AU  - Calco, G
AU  - Alharithi, Y
AU  - Phillips, E
AU  - Jacoby, D
AU  - Fryer, A
AU  - Maloyan, A
AU  - Nie, Z
TI  - Maternal high-fat diet increases airway sensory innervation and reflex bronchoconstriction in adult offspring
AID  - 10.1183/13993003.congress-2022.4397
DP  - 2022 Sep 04
TA  - European Respiratory Journal
PG  - 4397
VI  - 60
IP  - suppl 66
4099  - http://erj.ersjournals.com/content/60/suppl_66/4397.short
4100  - http://erj.ersjournals.com/content/60/suppl_66/4397.full
SO  - Eur Respir J2022 Sep 04; 60
AB  - Children born to obese mothers are prone to develop asthma and airway hyperresponsiveness, but the mechanisms behind this are unclear. Here, we developed a mouse model of diet-induced maternal obesity that recapitulates metabolic abnormalities seen in humans. Despite being fed a regular diet, adult offspring of high-fat diet fed mothers showed increased adiposity, hyperinsulinemia and insulin resistance. Bronchoconstriction induced by inhaled 5-hydroxytriptamine was significantly increased in offspring of high-fat diet vs. regular diet mothers. Increased bronchoconstriction was blocked by vagotomy, demonstrating that airway nerves mediate this reflex hyperresponsiveness. 3D confocal imaging of airway whole mounts show that offspring of high-fat diet mothers have increased epithelial sensory innervation and increased expression of neuronal substance P, compared with offspring of regular diet mothers. For the first time, we show that intrauterine exposure to maternal obesity increases airway sensory innervation in offspring, leading to reflex airway hyperresponsiveness.FootnotesCite this article as Eur Respir J 2022; 60: Suppl. 66, 4397.This article was presented at the 2022 ERS International Congress, in session “-”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).