# The Role of Androgens in Obesity Induced Meta-Inflammation

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $432,117

## Abstract

Project Summary/Abstract:
Obesity is a significant burden on society due to the high prevalence of obesity-induced diseases. Identifying
which obese individuals are at risk for metabolic and cardiovascular disease is a necessary step for
personalized treatment strategies. Male sex is a strong risk factor for metabolic and cardiovascular disease
and measures of chronic inflammation strongly link obesity to disease risk. Sex differences in metabolic
disease physiology, presentation, and treatment responses may relate to different inflammatory responses in
men and women. Therefore, we have been investigating the central concept that sex differences in metabolic
disease associated inflammation (meta-inflammation) contribute to the differential risk for diabetes between
obese men and women. The scientific premise for this model is based on the existing immunology literature
and our observations that male mice, but not females, have an exaggerated myeloid inflammatory response to
high fat diets that promotes the accumulation and activation of adipose tissue macrophages. Our preliminary
studies also show that castrated male mice have improved glucose metabolism and reduced adipose tissue
inflammation despite having increased adiposity compared to intact male controls. Based on these findings, we
will investigate the hypothesis that androgens promote meta-inflammation and impaired metabolism by
enhancing macrophage activation and myelopoiesis. We will test our hypothesis by completing two aims: Aim
1) To determine the mechanisms of androgen dependent adipose tissue macrophage activation and
insulin resistance in obesity. Aim 2) To determine the mechanism by which androgen receptor
signaling in myeloid progenitor cells and monocytes mediates obesity-induced inflammation.
Completing our aims will identify the cellular and molecular targets for androgen activity during obesity, leading
to sex differences in metabolic-induced inflammation. This project has the potential to close critical gaps in our
understanding of sex-differences and takes an innovative step-wise approach to understand androgen effects
on myeloid cell production, monocyte recruitment, and macrophage polarization during obesity.

## Key facts

- **NIH application ID:** 10149293
- **Project number:** 5R01DK115583-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kanakadurga Singer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $432,117
- **Award type:** 5
- **Project period:** 2018-07-11 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149293

## Citation

> US National Institutes of Health, RePORTER application 10149293, The Role of Androgens in Obesity Induced Meta-Inflammation (5R01DK115583-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10149293. Licensed CC0.

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