# Single Cell Characterization of Adipose Tissue in the Setting of HIV and Aging

> **NIH NIH K76** · YALE UNIVERSITY · 2022 · $226,556

## Abstract

Project Summary of Supplement:
Both the process of aging and HIV-infection are associated with pro-inflammatory environments that are
characterized by elevated levels of cytokines and inflammatory mediators. Stimulation of innate immune
receptors by both pathogen-associated molecular patterns and damage associated molecular patterns likely is
contributing to the systemic inflammation seen with advancing age, and HIV-infection. There is increasing
evidence that adipose tissue-derived inflammation likely contributes to this pro-inflammatory environment. Both
obesity and redistribution of adipose tissue occur with the process of aging and HIV-infection and are strongly
linked to metabolic syndrome. However, the mechanisms whereby adipose tissue contributes to the
development of metabolic syndrome are not fully understood. Adipose tissue is a cellular community that
includes adipocytes, endothelial cells, pre-adipocytes, and innate immune cells such as macrophages,
dendritic cells, and monocytes. The purpose of this proposal is to characterize both immune and non-
immune cell populations within adipose tissue using single cell RNA sequencing, in the context of
aging, and HIV-infection in order to understand how they contribute to systemic inflammation. In Aim 1,
fat pad biopsies will be collected from HIV-positive, and HIV-negative adults in the following age groups (21-
40) and (≥ 60 years). Multicolor flow cytometry and single cell RNA seq will be used to characterize both
immune (macrophages, dendritic cells, monocytes) and non-immune cell populations within adipose tissue by
evaluation of innate immune pathways, such as the NLRP3 inflammasome, cytokines (IL-1, IL-18, IL-6, TNF-
, IL-10 etc.), and transcriptomics of specific cells to evaluate cellular signaling networks and characterize new
cell populations. Aim 2 seeks to characterize protein expression in the context of adipose tissue architecture
by using CyTOF imaging mass cytometry. The supernatant of adipose tissue cell cultures will also be
collected and used to perform proteomic analysis of the secretome of adipose tissue cells in order to better
understand the inflammatory output of these cells. Clinical characteristics (e.g., BMI) and co-morbidities (e.g.,
diabetes) will be evaluated in conjunction with the experimental data. Our findings will allow us to better
understand the underlying innate immune mechanisms within specific cell populations that contribute to
adipose tissue derived inflammation and ultimately affect the pro-inflammatory environment that is seen in the
setting of aging, and HIV-infection.
2

## Key facts

- **NIH application ID:** 10613754
- **Project number:** 3K76AG064548-04S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Heidi J Zapata
- **Activity code:** K76 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $226,556
- **Award type:** 3
- **Project period:** 2019-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10613754

## Citation

> US National Institutes of Health, RePORTER application 10613754, Single Cell Characterization of Adipose Tissue in the Setting of HIV and Aging (3K76AG064548-04S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10613754. Licensed CC0.

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