# Depot-specific regulation of metabolism by adipose tissue stromal cell subpopulations

> **NIH NIH R56** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $232,826

## Abstract

Adipose tissue plays a central role in the pathogenesis of obesity-associated metabolic disease including type
2 diabetes (DM). Depot-specificity is a central feature of adipose tissue biology, as visceral adipose tissue
(VAT) is strongly linked to metabolic disease, while in contrast, subcutaneous adipose tissue (SAT) is
associated with metabolic health. Despite the importance of these disease associations, the mechanisms that
underlie depot-specific differences in adipose tissue function and their effect on systemic metabolism remain
poorly defined. Our preliminary data, based on single cell/single nuclear RNA sequencing and metabolic
phenotyping of human adipose tissue, identify distinct adipose tissue stromal cell (ASC) subpopulations in
human adipose tissue, including a visceral adipose tissue (VAT)-specific ASC subpopulation with inflammatory
features, and an adipogenic ASC subpopulation present in VAT and SAT. We also identify an important role for
the extracellular matrix (ECM) in regulating depot-specific differences in adipose tissue metabolism. The goals
of this proposal are to define the contribution of human ASC subpopulations to depot-specific differences in
adipose tissue metabolism, and their role in regulating systemic insulin resistance. We will test the central
hypothesis that an inflammatory VAT-specific ASC subpopulation mediates the adverse metabolic phenotype
of VAT and its detrimental effects on systemic metabolism, while absence of this VAT-specific ASC
subpopulation is responsible for the beneficial effects of SAT ASC on systemic metabolism; and that VAT and
SAT ECM have properties that control IM/FA-ASC balance and function, thus regulating depot-specific
differences in adipose tissue control of systemic metabolism. We will accomplish our goals using in vivo and in
vitro cellular metabolic phenotyping, innovative 2D and 3D human ASC-adipocyte-ECM culture systems, and
mouse human xenograft models to interrogate the role of ASC in regulating systemic metabolism. Completing
this translational science proposal will be significant because it will address a critical knowledge gap regarding
mechanisms that underlie depot-specific differences in adipose tissue function and its relation to systemic
metabolic disease, define ASC heterogeneity in humans and characterize novel ASC subpopulations
associated with insulin resistance, and elucidate the mechanisms by which these cell populations regulate
systemic metabolic disease.

## Key facts

- **NIH application ID:** 10685079
- **Project number:** 1R56DK132785-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Carey N Lumeng
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $232,826
- **Award type:** 1
- **Project period:** 2022-09-19 → 2024-09-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10685079

## Citation

> US National Institutes of Health, RePORTER application 10685079, Depot-specific regulation of metabolism by adipose tissue stromal cell subpopulations (1R56DK132785-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10685079. Licensed CC0.

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