# Reducing Pulmonary Inflammation in Obesity with Docosahexaenoic Acid

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $40,583

## Abstract

PROJECT SUMMARY
Significance. Pulmonary inflammation, which contributes toward the severity of lung diseases, is markedly
exacerbated by obesity. Thus, there is a need for novel therapeutic approaches for targeting pulmonary
inflammation in obesity. One promising strategy involves increased dietary consumption of docosahexaenoic
acid (DHA), an omega-3 polyunsaturated fatty acid, which exerts anti-inflammatory properties. The first step
toward developing DHA as a therapeutic for pulmonary inflammation in obesity is to establish the cellular targets
and mechanisms of this unique fatty acid. One key target of DHA is alveolar macrophages (AMs), which are
critical for maintaining respiratory homeostasis and drive pulmonary inflammation in obesity. Based on strong
preliminary data, we propose the central hypothesis that DHA targets AMs to improve the inflammatory
response through two key mechanisms. The first mechanism, tested in Aim 1, involves DHA esterification into
plasma membrane phospholipids of AMs and thereby controlling the biophysical organization of
sphingolipid/cholesterol-enriched lipid rafts to lower inflammatory signaling in obese mice. The second
mechanism, tested in Aim 2, involves DHA displacing arachidonic acid (AA) in the phospholipidome. AA is an
omega-6 PUFA which exerts pro-inflammatory effects through its conversion to hydroxylated derivatives such as
prostaglandins. Displacing AA with DHA would shift the balance from pro-inflammatory AA derivatives in obesity
to anti-inflammatory and pro-resolution DHA derivatives. One such DHA derivative is resolvin D1 (RvD1). RvD1
binds the G-protein coupled receptor ALX/FPR2 and decreases inflammation by driving macrophages to have
an anti-inflammatory phenotype. To test the central hypothesis, the applicant will rely on advanced imaging tools,
biochemical assays, and knockout mouse models including the innovative use of a newly generated myeloid
specific DHA-deficient mouse. Impact: The proposed studies will establish mechanisms by which DHA
improves pulmonary inflammation in obese mice and inform future clinical studies. This research will provide the
applicant with skills in developing and implementing rigorous study design, use of advanced laboratory
techniques (cutting-edge biophysical microscopy methods, flow cytometry, and biochemical assays), foster
interdisciplinary collaboration, and enhance leadership skills through writing, project management, and
mentoring. Ultimately, this will build the foundation for a successful biomedical research career.

## Key facts

- **NIH application ID:** 10997998
- **Project number:** 1F31HL176155-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Rafia Virk
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,583
- **Award type:** 1
- **Project period:** 2024-09-13 → 2027-03-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997998

## Citation

> US National Institutes of Health, RePORTER application 10997998, Reducing Pulmonary Inflammation in Obesity with Docosahexaenoic Acid (1F31HL176155-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10997998. Licensed CC0.

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