# Mechanisms mediating severity of acute pancreatitis in the aged

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2021 · $313,650

## Abstract

ABSTRACT
The objective of this project is to understand the mechanisms leading to the development of severe acute
pancreatitis (sAP), a life-threatening illness with high mortality characterized by necrotizing pancreas, severe
systemic inflammation, coagulation, multiple organ dysfunction syndrome (MODS). AP is a particularly serious
disease among the elderly as both incidence and the likelihood for progression to sAP increases dramatically
with advancing age. Despite recognition of this clinical problem, little is known regarding the underlying
biological mechanisms of this disease or why progression to sAP is more common among elderly patients. We
recently developed an aged mouse model of AP in which only aged mice exhibit sAP that parallels clinical
observations including prolonged systemic inflammation, coagulation, MODS, and fatality. Our observations
with this mouse model include a dramatic age-dependent increase in tissue damage and cytokine gene
expression within visceral adipose tissue, and elevated levels of free fatty acids in the ascitic fluid. Collectively
these findings suggest that visceral adipose tissues are key mediators promoting the progression of AP to sAP
in the aged. The central hypothesis of this project is that aged animals are more prone to develop sAP due to
pronounced visceral adipose tissue inflammation caused by leakage of pancreas-derived digestive enzymes
into the peritoneum from the damaged pancreas. AP-induced adipose tissue inflammation results in release of
free fatty acids, inflammatory cytokines, and pro-thrombotic factors, all promoting MODS. Our hypothesis will
be tested in the following three specific aims: To determine features of visceral adipose tissue inflammation in
aged animals with sAP (Aim 1); To demonstrate that increased visceral adipose tissue inflammation promotes
the progression of AP to sAP in the aged (Aim 2); and To develop strategies to prevent the progression of AP
to sAP in aged animals by suppressing adipose tissue inflammation (Aim 3).

## Key facts

- **NIH application ID:** 10169210
- **Project number:** 5R01AG055359-05
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Hiroshi Saito
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $313,650
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169210

## Citation

> US National Institutes of Health, RePORTER application 10169210, Mechanisms mediating severity of acute pancreatitis in the aged (5R01AG055359-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10169210. Licensed CC0.

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