# Compromised Resolution of Inflammation following Nanoparticle Exposure in Metabolic Syndrome

> **NIH NIH R01** · PURDUE UNIVERSITY · 2022 · $337,723

## Abstract

Project Summary / Abstract
Individuals with metabolic syndrome (MetS) compose a significant and growing proportion of our U.S. and global
population (> 25%). It has been established that the presence of chronic diseases, such as MetS, enhances and
prolongs environmental exposure-induced inflammation. Individuals with MetS have demonstrated enhanced
inflammation due to ambient particulate matter exposures of which a significant proportion is nano-sized. The
mechanisms associated with this enhanced susceptibility represent a significant gap in our knowledge. Mounting
data from the Shannahan laboratory suggests that dysregulation of inflammatory resolution contributes to the
exacerbated toxicity and disease progression observed in MetS. Specifically, nanoparticle inhalation exposures
induce a pulmonary inflammatory response that is exacerbated and extended due to MetS. This inflammatory
response corresponds with suppression of specialized pro-resolving mediators that facilitate inflammatory
resolution. Our data suggests following inhalation, nanoparticles gain unique biocoronas on their surface that
enhance the pro-inflammatory response while inhibiting resolution signaling. Further, our preliminary data
demonstrates MetS disrupts ω-3 fatty acid metabolism impairing resolution. This proposal examines the
hypothesis that dysregulation of inflammatory resolution following nanoparticle exposure mediates the
susceptibility observed in MetS by exacerbating inflammatory responses and facilitating development and
progression of chronic disease. The hypothesis will be tested through the completion of three main goals: 1)
Delineation of pulmonary nanoparticle-biocorona alterations throughout metabolic syndrome development and
the inflammation signaling consequences; 2) Determination of inflammatory resolution and specialized pro-
resolving mediator kinetics following nanoparticle exposure in MetS and healthy mouse models; 3) Elucidation
of differential ω-3 fatty acid metabolism in MetS following nanoparticle exposure. These mechanisms represent
potential key regulators that are dysregulated in MetS, facilitating exacerbated responses and also are potential
targets of therapeutic interventions. Typically, research and treatment strategies addressing exposure-induced
inflammation focus on suppression of pro-inflammatory pathways rather than elucidation and effective
stimulation of resolution processes. Completion of the project will generate new knowledge required to
understand distinct mechanisms of toxicity in prevalent and sensitive subpopulations such as MetS. Elucidation
of these mechanisms will allow for new disease prevention and treatment strategies while also broadening public
health protections to environmental exposures.

## Key facts

- **NIH application ID:** 10441741
- **Project number:** 1R01ES033173-01A1
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Jonathan Henry Shannahan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $337,723
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10441741

## Citation

> US National Institutes of Health, RePORTER application 10441741, Compromised Resolution of Inflammation following Nanoparticle Exposure in Metabolic Syndrome (1R01ES033173-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10441741. Licensed CC0.

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