# Adipose Tissue Macrophage Phenotype and Function

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $563,710

## Abstract

The ability of adipose tissue to efficiently store and release lipid is critical for mammals to maintain metabolic
health. In conditions when triglyceride storage by adipocytes is impaired lipid accumulates ectopically in non-
adipocytes and is associated with common systemic disorders including type 2 diabetes, non-alcoholic fatty liver
disease, susceptibility to infections, atherosclerosis, dementia and autoimmune disorders. Although the
pathways that regulate systemic release of lipids via lipolysis and the uptake of fatty acids and carbohydrates for
lipogenesis have long been known and are well studied, our understanding of local lipid homeostasis in fat is
largely unexplored. Studies originally funded by the grant found that macrophages and other immune cells
accumulate in adipose tissue in response to changes in metabolic state and that the adipose tissue macrophages
have a unique phenotype and ability to handle and metabolism lipid. In studying the source of lipid in adipose
tissue macrophages, we discovered a lipase-independent pathway of lipid release by adipocytes, in which acyl-
glycerides are incorporated into extracellular vesicles (AdExos) and released at a high rate that correlates with
adipose tissue macrophage content and lipolysis. During the current funding cycle we published these findings
and described basic aspects of AdExos biology including their rate of release by adipocytes and regulation by
adiposity, uptake by ATMs via macropinocytosis, ability to induce chemotaxis in bone marrow derived
macrophages and to activate a program of lipid metabolism typical of authentic ATMs. From these findings we
hypothesize AdExos are the key interface between the metabolic and immune systems in fat and a central
component of lipid homeostasis in adipose tissue. In the current proposal, we set out to determine whether
AdExos regulate the recruitment, differentiation and proliferation of monocyte-derived and resident ATMs, test
whether the differential response to AdExo of monocyte derived and resident ATMs account for differences in
inflammatory and trophic phenotypes, determine whether a lipolysis per se drives AdExo production and test if
ATM hydrolysis of lipids in AdExos contribute to a lipid cycle in adipose tissue.

## Key facts

- **NIH application ID:** 10833172
- **Project number:** 5R01DK066525-20
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Anthony W Ferrante
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $563,710
- **Award type:** 5
- **Project period:** 2003-09-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833172

## Citation

> US National Institutes of Health, RePORTER application 10833172, Adipose Tissue Macrophage Phenotype and Function (5R01DK066525-20). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10833172. Licensed CC0.

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