# Adipocyte-derived exosomes in macrophage regulation

> **NIH NIH F30** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $46,060

## Abstract

Project Summary
 Obesity is a common condition that is associated with poor health outcomes, and a significant portion of
these pathologies are mediated by dysfunction and dysregulation of adipose tissue at a cellular and molecular
level. Adipose tissue contains a unique population of macrophages (adipose tissue macrophages, or ATMs).
These ATMs accumulate in obesity and mediate a number of key processes and pathologies in adipose tissue,
including lipid handling, inflammation, and insulin resistance. Multiple populations of ATMs exist: a tissue-
resident, anti-inflammatory population is descended from yolk sac embryonic hematopoietic progenitors and is
present at all times; a pro-inflammatory population is derived from circulating monocyte precursors in adults
and is recruited under conditions of metabolic stress such as obesity. Exosomes are small, secreted,
endosome-derived, membrane-bound extracellular vesicles. Adipocytes constitutively release lipid-containing
exosomes (adipocyte-derived exosomes, or AdExos), and the rate of their secretion is increased during states
of increased ATM accumulation, including obesity and acute fasting. AdExos can also act as macrophage
chemoattractants and drive reprogramming of bone marrow-derived macrophages toward an ATM-like
transcriptional and phenotypic identity. However, many questions regarding the full scope and effects of
AdExos remain unaddressed. We hypothesize that AdExos regulate the accumulation and differentiation of
macrophages in adipose tissue via pathways canonically known to regulate ATMs. Given that AdExo
production is increased in conditions during which monocyte recruitment and ATM recruitment occurs, and that
AdExos both act directly as macrophage chemoattractants and drive production of monocyte chemoattractant
factors in adipose tissue, we believe that AdExos regulate monocyte recruitment to adipose tissue. Aim 1
seeks to establish this role in an in vivo setting by monitoring the effect of direct AdExo injection on
chemoattraction and accumulation of monocytes. Previous work has examined the effect of AdExos on the
identity of bone marrow-derived macrophages, but not more relevant precursors such as yolk sac
hematopoietic progenitors and peripheral monocytes. Aim 2 seeks to test the relationship between progenitor
cell identity and the effect of AdExo exposure on cell fate. While we have established that AdExos may play a
role in both ATM recruitment and ATM identity, we do not know the mechanisms that govern these actions.
Aim 3 seeks to test whether pathways known to canonically regulate ATM differentiation and identity, like the
CCR2 axis and PPARG, respectively, are also responsible for the AdExo-mediated regulation of these
processes in ATMs.

## Key facts

- **NIH application ID:** 10388517
- **Project number:** 1F30DK129008-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Joshua Harrison Goodman
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,060
- **Award type:** 1
- **Project period:** 2021-09-15 → 2025-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388517

## Citation

> US National Institutes of Health, RePORTER application 10388517, Adipocyte-derived exosomes in macrophage regulation (1F30DK129008-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10388517. Licensed CC0.

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