# The role of circulating meta-inflammatory monocytes in adolescent insulin resistance

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $99,999

## Abstract

ABSTRACT
Adults with obesity have increased myeloid inflammatory responses that associate with cardiovascular and
metabolic disease. There are several gaps, though, in our current understanding of metabolic inflammation
(meta-inflammation) including our understanding of initiating changes in myelopoiesis and regulated changes
in myeloid cells. It is clear that some individuals develop a meta-inflammatory response placing them at higher
risk for metabolic impairment while others are protected. While it is clinically important to identify adolescents
at risk for future disease, we do not understand how to use meta-inflammatory markers to assess disease risk.
Our previous human and mouse studies demonstrate that individuals who expand inflammatory monocytes in
response to obesogenic diets are at greatest risk for metabolic disease. Based on the ability of these
monocytes to generate an inflammatory response, traffic to tissues and differentiate into inflammatory tissue
macrophages promoting insulin resistance, we are terming them meta-inflammatory monocytes (MiMo). Given
that animal models and clinical studies have demonstrated that myeloid inflammation with circulating cytokines,
enhanced circulating myeloid cells and tissue inflammation are linked with insulin resistance it is critical to
understand if these same mechanisms exist in adolescents and can differentiate who is at risk for future
metabolic disease. The goals of the primary proposal investigate the central hypothesis that adolescents at
risk for metabolic disease have an increase in MiMos and enhanced MiMo recruitment, cytokine secretion and
macrophage polarization leading to insulin resistance. We will evaluate this hypothesis in three aims: Aim 1)
To define the monocyte transcriptomic signatures associated with metabolic disease in adolescents. Aim 2) To
determine high risk and low risk monocyte phenotypes produced in adolescents with metabolic impairment.
Aim 3) To assess meta-inflammatory monocyte activation and metabolism in response to dietary fatty acid
stimulation. This supplement keeps with the same primary goals of the project but would allow us to expand
the inclusion of gender minority adolescents with gender dysphoria on post-pubertal sex hormone modulating
therapies. This will further the translation of our findings to these clinical populations of adolescents.

## Key facts

- **NIH application ID:** 11018656
- **Project number:** 3R01DK130864-03S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kanakadurga Singer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $99,999
- **Award type:** 3
- **Project period:** 2022-08-01 → 2025-03-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11018656

## Citation

> US National Institutes of Health, RePORTER application 11018656, The role of circulating meta-inflammatory monocytes in adolescent insulin resistance (3R01DK130864-03S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/11018656. Licensed CC0.

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