# Role of IRF3 in Energy and Glucose Homeostasis

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2022 · $661,923

## Abstract

ABSTRACT
Obesity and Type 2 diabetes represent states of chronic inflammation. While we have learned
much about how the soluble mediators and signaling intermediates of immunity disrupt normal
metabolic function, we do not yet understand the transcriptional mechanisms by which these
responses occur. Our laboratory has discovered that interferon regulatory factors (IRFs), a family
of immune-related transcription factors, are active in tissues of metabolic relevance. We showed
that IRF3 in particular becomes induced during obesity, and mediates many of the adverse effects
of overnutrition, including weight gain, suppression of brown fat function, insulin resistance, and
hepatic steatosis. We have gone on to show that IRF3 exerts distinct functions in adipocytes and
hepatocytes, with differential effects on metabolic parameters. We also identify a key downstream
IRF3 target, ISG15, as a mediator of the actions of IRF3 in fat. In the current proposal, we will
advance our knowledge of IRF3 and metabolic function by focusing on its actions in
macrophages, specifically in adipose tissue macrophages and Kupffer cells of the liver.
Furthermore, we will determine the mechanisms by which ISG15 represses adipose browning
and thermogenesis. Finally, we will pursue an unbiased analysis of IRF3 target genes in fat, liver,
and macrophages, to determine new pathways at the nexus of metabolism and inflammation that
may be amenable to therapeutic intervention.

## Key facts

- **NIH application ID:** 10477318
- **Project number:** 5R01DK102170-08
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Evan D Rosen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $661,923
- **Award type:** 5
- **Project period:** 2015-04-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477318

## Citation

> US National Institutes of Health, RePORTER application 10477318, Role of IRF3 in Energy and Glucose Homeostasis (5R01DK102170-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10477318. Licensed CC0.

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