# Inflammatory Responses of The Visceral Adipose Tissue Microcirculation

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $477,058

## Abstract

PROJECT SUMMARY / ABSTRACT
The expanding fat depots of overweight and obese individuals experience pathologic leukocyte infiltration, a
process that takes place in the microcirculation of organ tissue. Thus, the visceral adipose depots become
inflamed, dysfunctional and contributes to insulin resistance, cardiovascular disease, cancer and arthritis,
whose incidence is gaining in the ever-growing obese population of the USA. The precise time-course and
mechanisms by which excessive calorie intake instigates leukocyte infiltration in expanding adipose depots
remain undefined, which limits therapeutic interventions in obese humans. Published work, along with new
preliminary data presented here, uncover a novel role for the endothelium of the adipose tissue
microcirculation in these processes. Our preliminary data demonstrate a mechanistic role for the calcium-
dependent cysteine protease calpain in post-prandial infiltration of circulating leukocytes into visceral fat
depots. Our working hypothesis is that lipids overload causes post-prandial activation of
endothelial-expressed calpain via transactivation of the EGF receptor, with subsequent
upregulation of leukocyte-endothelium interactions in the microcirculation of the visceral fat
depots. As a result, adipose tissue is subjected to the inflammatory action of infiltrating
leukocytes. The long-term goals of this project are: 1) to understand the molecular and cellular determinants
that makes the microcirculation of visceral fat highly responsive to post-prandial absorption of macronutrients;
2) to investigate the signaling pathways responsible for post-prandial activation of endothelial calpain; 3) to
study the impact of these processes on the postprandial and chronic inflammatory responses of the adipose
tissue. Toward these goals, we will utilize knockout and transgenic mouse technology along with the following
physiology and biochemistry techniques: intravital microscopy, cells and tissue isolation procedures, western
blot analysis, immunohistochemistry and immunofluorescence, interfering RNA technology. We hope that the
results of this work will advance our understanding of the integrated mechanisms that initiate and maintain
adipose tissue inflammation and related disorders in the overweight/obese organism.

## Key facts

- **NIH application ID:** 9906206
- **Project number:** 5R01DK111042-04
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** SATORU EGUCHI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $477,058
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906206

## Citation

> US National Institutes of Health, RePORTER application 9906206, Inflammatory Responses of The Visceral Adipose Tissue Microcirculation (5R01DK111042-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9906206. Licensed CC0.

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