# Mechanisms of airway hyperresponsiveness in the offspring of obese mothers

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $581,204

## Abstract

Project Summary:
Offspring of obese mothers are more likely to develop asthma, although the exact molecular mechanisms that
determine this relationship remain unclear. We recently have developed a mouse model of maternal obesity that
recapitulates metabolic abnormalities seen in offspring seen in humans. Despite being fed solely a regular diet,
offspring of obese mother developed hyperinsulinemia, airway epithelium hyperinnervation and reflex airway
hyperresponsiveness. Changes in both parasympathetic and sensory nerves are believed to contribute to this
hyperresponsiveness. We have previously reported that hyperinsulinemia reduces M2 muscarinic receptor
function on airway parasympathetic nerves causing increased acetylcholine release and potentiating
parasympathetic nerve-induced bronchoconstriction. It also has been reported that insulin promotes neurite
outgrowth, and we have previously shown that increased sensory innervation correlates with disease severity in
patients with asthma. Based on these findings, we hypothesize that intrauterine exposure to maternal
obesity increases airway innervation and subsequent airway hyperresponsiveness in an insulin-
dependent manner. In this project, we will characterize changes in airway neuronal structure and function,
neurotransmitter expression, as well as the role of insulin in these changes, by testing the following three specific
aims. First, we will test the effect of maternal obesity on airway sensory and parasympathetic nerve function in
offspring. Second, we will test the effect of maternal obesity on neuronal architecture, neurotransmitter content
and M2 receptor expression in nerves of the offspring. Finally, we will determine the role of insulin in airway
hyperresponsiveness and hyperinnervation in the offspring of obese mothers. This project uses cutting edge,
innovative techniques developed in our labs and will significantly increase our understanding of the mechanisms
of asthma in adult offspring of obese mothers, which will guide us to develop new strategies for specific
prevention and treatment in this population.

## Key facts

- **NIH application ID:** 10841576
- **Project number:** 5R01HL164474-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Alina Maloyan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $581,204
- **Award type:** 5
- **Project period:** 2022-06-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841576

## Citation

> US National Institutes of Health, RePORTER application 10841576, Mechanisms of airway hyperresponsiveness in the offspring of obese mothers (5R01HL164474-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10841576. Licensed CC0.

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