# Developmental lineages and functions of macrophages in white adipose tissue

> **NIH NIH K99** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $90,000

## Abstract

ABSTRACT: Adipose tissue-associated disorders including obesity, lipodystrophy, and cancer-associated fat
wasting collectively account for 1 in 4 deaths in the United States (1-3). Despite the devastatingly high number
of deaths, therapeutic options remain limited and unsatisfactory. Landmark studies since the 1990’s have
established that accumulation and activation of macrophages in adipose tissues are linked to inflammation,
insulin resistance, and type 2 diabetes (4-20). However, the roles of adipose tissue macrophages outside tissue
inflammation remain poorly understood. This is particularly important, as studies suggest that adipose tissue
macrophages may be involved in fat development (21-23), fat storage (24), and protection against fat wasting
(25). Our preliminary data published in Science (26) demonstrate that embryo-derived adipose tissue resident
macrophages promote lipid storage in adipocytes via production of PDGFcc. This process is independent from
inflammation and insulin resistance promoted by bone-marrow-derived macrophages.
 Our preliminary data in (Aim 1) suggest that macrophages are required for fat loss. Therefore, in Aim 1 I will
delineate the responsible macrophage lineages (K99) and identify macrophage-dependent mechanisms (R00)
that control fat mobilization/loss. In (Aim 2), I will determine the transcriptional basis for control of lipid storage
by adipose tissue resident macrophages using single nucleus RNA-sequencing (K99). I expect to deduce
changes in cellular circuitries and downstream signaling pathways that control fat storage. The candidate
molecules identified here will be explored in the R00 phase of this research using human fat organoids and in
vivo mouse models. In (Aim 3), I will use human fat organoids that contain human resident-like macrophages
to confirm the role of PDGFcc in fat storage in humans (K99). I have found that human fat organoids that contain
Pdgfc+ resident-like macrophages accumulate more lipids as compared to macrophage-less fat organoids. I will
(R00) use these fat organoids to determine how macrophages affect lipid metabolism and identify whether
macrophages act directly on adipocytes. Additionally, human organoids will be used to screen for macrophage-
dependent mediators of energy storage identified in Aims 1 and 2. I will continue to be mentored by Dr Frederic
Geissmann, a leader in the field of macrophage biology.
The Geissmann lab is among the first to characterize
the developmental lineages and functions of macrophages. I will also benefit from the expertise of my advisory
committee that includes Anthony Ferrante, Chris Glass, and Olivier Elemento. Drs. Chris Glass and Olivier
Elemento are highly respected scientists with expertise in analysis of macrophages and white adipose tissues
by single cell methodologies. Whereas, Drs Anthony Ferrante is an expert in the areas of myeloid cell biology,
metabolism, and adipose tissue function. My expectations are that this proposal combined ...

## Key facts

- **NIH application ID:** 10449634
- **Project number:** 1K99DK131280-01A1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Nehemiah Cox
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $90,000
- **Award type:** 1
- **Project period:** 2022-05-15 → 2023-02-27

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449634

## Citation

> US National Institutes of Health, RePORTER application 10449634, Developmental lineages and functions of macrophages in white adipose tissue (1K99DK131280-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10449634. Licensed CC0.

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