# MiR-23/27/24 Control of Adipose Tissue Macrophage Activation

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $265,223

## Abstract

SUMMARY
Macrophages are the most abundant inflammatory cell in obese adipose tissue. And it is well established in
animal models that the pro-inflammatory cytokines they produce drive systemic metabolic dysfunction including
insulin resistance, which is a major cause of morbidity and mortality in overweight individuals. Emerging
evidence suggest that this activation program differs from classic macrophage activation in response to
bacterial components, therefore offering the potential for targeted therapies to uncouple obesity from disease
through the selective inhibition of macrophage function. Discovering the molecular pathways that regulate this
unique program of activation are key to both understanding this basic facet of macrophage biology as well as
leveraging it to therapeutic advantage. In preliminary data, we have found that the clusters of microRNAs
(miRNAs) containing miR-23, miR-24 and miR-27 regulate the production of pro-inflammatory cytokines in
culture conditions that model the obese adipose tissue microenvironment. The aims proposed in this grant will
determine the function of this cluster of miRNAs in obese adipose tissue macrophages as well as define the
network of genes regulated by these miRNAs in macrophages. We will use well-established diet induced
obesity mouse models with newly generated miRNA conditional knock out mice as well as state-of-the-art
approaches in RNA biology to investigate the unique cellular and molecular mechanisms that regulate these
macrophages. Obesity affects nearly 40% of the adult population of the US and increases the risk of diabetes,
cardiovascular disease and cancer. Ultimately, strategies including the use of RNA therapeutics to target
miRNAs and their gene networks could offer a novel approach to modify macrophage function to control
obesity-associated inflammation and mitigate the effects of associated chronic diseases.

## Key facts

- **NIH application ID:** 10109910
- **Project number:** 1R21AI156292-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Heather H Pua
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $265,223
- **Award type:** 1
- **Project period:** 2021-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109910

## Citation

> US National Institutes of Health, RePORTER application 10109910, MiR-23/27/24 Control of Adipose Tissue Macrophage Activation (1R21AI156292-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10109910. Licensed CC0.

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