# Adipose Tissue Macrophage Control of Metabolic Dysfunction in Diabetes

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $581,816

## Abstract

PROJECT SUMMARY
Obesity-induced inflammation is a well-established mechanistic link between obesity and diabetes. Adipose
tissue macrophages (ATMs) lie at the center of the adipose tissue immune network. Many knowledge gaps
exist regarding ATM biology and its relationship to human metabolic disease. The mechanisms of ATM
accumulation, how their activation state relates to type 2 diabetes mellitus (DM), and how they communicate
with preadipocytes and adipocytes to regulate nutrient storage are incompletely understood. The goal of this
proposal is to address these knowledge gaps using complementary studies in human adipose tissue samples
and mouse models. The scientific premise for the hypotheses in this project is rooted in the observation from
our groups that visceral adipose tissue from obese (DM) subjects have higher CD206+ ATMs, fewer
preadipocytes, larger adipocytes, and manifest adipocyte metabolic dysfunction compared to obese non-DM
subjects. We propose a model whereby the expansion of CD206+ ATMs by in situ proliferation blocks
preadipocyte proliferation and differentiation to generate a dysfunctional adipose tissue environment. We will
evaluate CSF1 as a putative activator of CD206+ ATMs in humans and evaluate the function of CCL18 as a
CD206+ ATM secreted chemokine that mediates ATM-preadipocyte communication. If completed our proposal
will significantly advance our understanding of how human metabolic inflammation develops independent of
obesity and lead to substantial revisions in the current models of ATM function.
To evaluate our model, we propose to complete three specific aims: 1) To define mechanisms of CD206+
hATM proliferation and its relationship to adipocyte hypertrophy and DM status. 2) To identify mechanisms
underlying CD206+ ATM-preadipocyte crosstalk and resultant preadipocyte and adipocyte metabolic
dysfunction. 3) To evaluate the role of ATM-derived CCL18 in the regulation of adipose tissue inflammation
and metabolism. The experimental approach for all aims utilize tissue samples from a large bariatric surgery
cohort with diversity in age and sex, and assays of inflammatory and metabolic function. This study will
accomplish its goals using a team science approach between surgeons and basic scientists to close the gap
between our understanding of metainflammation in human and murine models. If completed our study can
impact health by identifying new biomarkers for DM risk independent of obesity and new pathways for
therapeutic interventions.

## Key facts

- **NIH application ID:** 9968313
- **Project number:** 5R01DK115190-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Carey N Lumeng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $581,816
- **Award type:** 5
- **Project period:** 2017-07-18 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968313

## Citation

> US National Institutes of Health, RePORTER application 9968313, Adipose Tissue Macrophage Control of Metabolic Dysfunction in Diabetes (5R01DK115190-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9968313. Licensed CC0.

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