# Visceral fat gamma delta T cells in sepsis pathogenesis

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2022 · $320,000

## Abstract

ABSTRACT
Sepsis pathophysiology involves activation of both pro- and anti-inflammatory responses, along with alterations
in thrombotic and metabolic pathways. We previously revealed that genes for several inflammatory and
thrombotic mediators are highly expressed in visceral adipose tissues during sepsis; however, what causes the
fat tissue to be so reactive and whether adipose-derived factors are mediators of sepsis is currently not known.
Our preliminary data using both a preclinical mouse model of sepsis, as well as, patient-derived samples
suggest that visceral fat is the major source of plasminogen activator inhibitor type 1 (PAI-1), a pro-thrombotic
factor which is implicated in the pathogenesis of sepsis and multi-organ failure. In addition, we recently found
that gamma delta (γδ)-T cells, a subset of innate-like T cells, are surprisingly abundant in visceral fat tissue.
These findings have led to our hypothesis that these cells are responsible for PAI-1 overproduction by adipose
tissues during sepsis and contribute to the development of organ injury. The major goals of this project are (1)
to demonstrate that γδ-T cells are key regulators of PAI-1 production in visceral fat tissue, and (2) to establish
that visceral fat-derived PAI-1 promotes organ injury during sepsis. To achieve these goals, a series of ex vivo
adipose explant culture experiments utilizing tissues from several transgenic mouse strains will be performed,
and visceral fat tissues will be surgically removed or transplanted from wild-type to PAI-1 knockout mice.
Completion of this project will establish the concept that overproduction of PAI-1 from visceral fat contributes to
the pathophysiology of sepsis-associated organ injury and reveal key mechanisms for PAI-1 overproduction.
This information will aid in the development of future therapeutic strategies to reduce sepsis severity.

## Key facts

- **NIH application ID:** 10409752
- **Project number:** 5R01GM129532-05
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Marlene Elena Starr
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $320,000
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10409752

## Citation

> US National Institutes of Health, RePORTER application 10409752, Visceral fat gamma delta T cells in sepsis pathogenesis (5R01GM129532-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10409752. Licensed CC0.

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