# Mechanisms that Direct Airway Remodeling in Obese Asthma

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $486,520

## Abstract

Project Summary
Chronic asthma affects millions of people in the United States, and nearly 40% of the asthma patient
population is obese and exhibit increased asthma symptoms and severity. Obesity is associated with
inflammatory and metabolic changes that can contribute to asthma pathobiology. Specifically, systemic
metabolic changes in the obese patient, including increased levels of leptin, a pro-inflammatory mediator
secreted by adipose tissue, and decreased responsiveness to glucagon-like peptide 1 (GLP-1), a gut hormone
that regulates insulin production may augment pathogenic processes in asthma by acting directly on structural
cells in the airway. Airway remodeling describes airway structural changes in asthma that can result in
permanent airway obstruction. Airway fibroblasts contribute to this process by migrating to the sub-mucosa,
where they proliferate and secrete extracellular matrix. The mechanisms directing airway remodeling in obese
asthma are particularly poorly understood, but in allergic asthma, airway remodeling is directed in part by the
key TH2 cytokine, interleukin-13 (IL-13). We have shown that IL-13 significantly stimulates airway fibroblast
invasion in asthma compared with non-asthma subjects and that this effect is augmented in obese patients.
Preliminary data that we present here suggest that leptin enhances airway fibroblast invasion and matrix
production and that GLP-1 blocks these effects. Our overarching hypothesis is that leptin and GLP-1 play an
important role in the development of airway fibrosis in allergic asthma, providing a link between obesity,
glucose metabolism and asthma. The studies described in this proposal will test this hypothesis by identifying
the mechanism of leptin-directed pro-fibrotic responses in airway fibroblasts in obese asthma (Aim 1), defining
the role of GLP-1 in blocking allergen-induced airway fibrotic processes (Aim 2) and, determine the impact of
bariatric surgery and weight loss on airway fibrosis in obese asthma (Aim 3). Successful completion of these
Aims will not only increase our understanding of the unique cellular and metabolic mechanisms directing the
pathobiology of obese asthma, but will also test specific interventions to treat obese asthma patients.

## Key facts

- **NIH application ID:** 9970287
- **Project number:** 5R01HL130234-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Jennifer L. Ingram
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $486,520
- **Award type:** 5
- **Project period:** 2017-09-18 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970287

## Citation

> US National Institutes of Health, RePORTER application 9970287, Mechanisms that Direct Airway Remodeling in Obese Asthma (5R01HL130234-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9970287. Licensed CC0.

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