# Interleukin-13 in Central Regulation of Metabolism

> **NIH NIH F30** · TUFTS UNIVERSITY BOSTON · 2024 · $46,918

## Abstract

PROJECT SUMMARY
The immune system is an important and dynamic regulator of metabolism. In peripheral tissues, over-nutrition
and obesity lead to marked changes in immune cell population, causing associated shifts in signaling and
tissue function. While type I immunity is associated with the release of pro-inflammatory cytokines and insulin
resistance, type II immunity has been shown to promote beige fat biogenesis, glucose homeostasis, and
energy balance. In the brain, activation of the pro-inflammatory NF-kB signaling pathway can lead to
hyperphagia and metabolic dysfunction. Whether activation of type II immune signaling pathways can restore
energy balance and protect against obesity has not yet been investigated. IL-13 is a Th2 cytokine that signals
through its cellular receptor IL-13R1. Whole body deletion of Il13ra1 causes obesity and loss of blood glucose
homeostasis. Il13ra1 is expressed in the subtantia nigra and ventral tegmental area of the brain. Preliminary
data show that specific deletion of Il13ra1 from the dopaminergic midbrain at least partially reproduces the
metabolic phenotypes of the whole-body knockout. The substantia nigra and ventral tegmental area are the
primary producers of dopamine in the CNS. Numerous studies have related central dopamine activity to energy
balance. In this study, we will test the hypothesis that central IL-13 signals through its receptor in the
dopaminergic midbrain to maintain energy balance. We will investigate the cellular and molecular mechanisms
by which it does so. We will use both gain-of-function and loss-of-function genetic models to test our
hypothesis. Knowledge from this study is expected to fill major gaps in our understanding of how the immune
system interacts with the nervous system to coordinate metabolic regulation, and also to identify novel
pathways in the CNS that modulate energy balance.

## Key facts

- **NIH application ID:** 10886000
- **Project number:** 5F30DK128884-04
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Mayer Marc Chalom
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $46,918
- **Award type:** 5
- **Project period:** 2021-08-16 → 2025-05-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886000

## Citation

> US National Institutes of Health, RePORTER application 10886000, Interleukin-13 in Central Regulation of Metabolism (5F30DK128884-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10886000. Licensed CC0.

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