# Spatial context of adipose tissue macrophages in obesity

> **NIH NIH R03** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $117,000

## Abstract

PROJECT SUMMARY
Adipose tissue inflammation is a known link between obesity and metabolic dysfunction and is associated with
accumulation of adipose tissue macrophages (ATM). However, the interplay between ATMs and obese tissue
inflammation and tissue expansion is still not well understood. Unbiased techniques such as RNA-sequencing
of whole tissue or single cells have been extremely useful in characterizing adipose tissue cellular changes with
obesity, though these methods lose anatomical context. The fine detail of tissue architecture and ATMs within
their anatomical niche is a critical aspect of understanding their function in vivo, but methods such as
immunolabeling can only detect a small subset of known markers and structures. Here I propose to use the
recently available method of spatial transcriptomics (STX) to capture gene expression signatures across adipose
tissue, retaining anatomical context of cell signatures and near single cell resolution. My preliminary data validate
the feasibility of this approach for adipose tissue and identify lysosomal signatures in scavenger receptor high
(SRhi) ATMs as a high priority target for investigation in obesity and diabetes. In conjunction with STX, I will
perform single cell transcriptomics to delineate representative ATM and adipocyte signatures, which I will use to
generate spatial maps of ATM-adipocyte niches during obesity. My overall goal is to map SRhi and SRlo ATM
niches within adipose tissue in metabolic dysfunction. My central hypothesis is that dysfunctional lysosomal
processing during SRlo ATM clearance of dying adipocytes precedes internal lipid accumulation and aggregation
into proinflammatory crown-like structures (CLS). To examine this hypothesis, I will investigate ATMs and
adipocytes in STX and single cell transcriptomics data and ATM lysosomal function in a time course of murine
obesity. My research aims are: (1) Identify ATM niches and their lysosomal signatures in obese adipose tissue.
I will examine the hypothesis that the anatomical niche of SRlo ATMs promotes lysosomal stress during interface
with apoptotic adipocytes prior to CLS formation. Single cell transcriptomics will enable identification of prominent
ATM subsets across the time course, and I will map these signatures to specific anatomical locations within
adipose tissue. (2) Determine lysosomal function, lipid accumulation, and proinflammatory cytokine production
in SRhi and SRlo ATMs. I will examine the hypothesis with increased duration of obesity, lysosomal stress in SRlo
ATMs associates with lipid accumulation and production of proinflammatory mediators prior to development of
insulin resistance. To determine lysosomal signatures and function, lipid-laden vs. lipid-lo ATMs from the time
course will be examined through bulk RNA-sequencing, lysosomal staining and quantification, and assays to
identify mediators of lysosomal stress and lipid accumulation. The proposed work develops a new line of my
research focusi...

## Key facts

- **NIH application ID:** 10438853
- **Project number:** 5R03DK129636-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Lindsey Allison Muir
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $117,000
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438853

## Citation

> US National Institutes of Health, RePORTER application 10438853, Spatial context of adipose tissue macrophages in obesity (5R03DK129636-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10438853. Licensed CC0.

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