# Postprandial activation of hyaluronan-MARCO axis contributes to systemic chronic inflammation

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $416,464

## Abstract

PROJECT SUMMARY/ABSTRACT
Systemic chronic inflammation (SCI) is a common comorbidity of type 2 diabetes (T2D) and
inflammatory bowel disease (IBD), e.g., it affects 25-40% of IBD patients, contributing to
extraintestinal manifestations of IBD. The contribution of postprandial inflammation to the SCI in
those contexts remains unclear. Our preliminary data in T2D patients suggest hyaluronan (HA)
correlates with plasma inflammatory cytokines, and postprandial HA is much higher in T2D
patients, which can be quickly normalized by bariatric surgery. We modeled this postprandial
HA spike in diet-induced obese animal models, and we found this phenomenon was more
pronounced in IBD mouse models. With a new Has2 overexpression mouse model we
generated in a recent publication studying adipose tissue HA, we found circulating HA can
induce hepatic macrophage receptor with collagenous structure (Marco) expression. MARCO
belongs to class A scavenger receptors. MARCO itself is not capable of eliciting inflammation,
but may function with intracellular pattern recognition receptors to stimulate an inflammatory
response. With new mouse models to either delete Marco or overexpress Marco, we showed it
augmented postprandial inflammatory response, and required nucleotide-binding
oligomerization domain containing 1 (NOD1) in this process. Based on these data, we
hypothesize that meal induces quick displacement of HA from the intestinal tract, entering the
circulation to induce Marco expression on liver macrophage – Kupffer cells (KCs). Saturated
fatty acids from the diet use MARCO to be delivered into the cell to activate NOD1 to elicit an
inflammatory response. With several genetically engineered mouse models, we will examine
(A). the mechanism by which HA promotes Marco expression in KCs; (B) the role of liver
macrophage Marco in cytokine secretion; (C) the source of inflammatory stimuli and the direct
effector of KCs inflammatory response in three specific aims. Aim 1 will determine the role of HA
in postprandial hepatic KC Marco expression; Aim 2 will determine the molecular mechanism by
which KC MARCO enhances postprandial inflammation and contributes to SCI; and Aim 3 will
evaluate whether digesting HA or neutralizing MARCO alleviates SCI and related pathologies.
Completing the proposed research will provide novel scientific knowledge on the HA-MARCO
axis in postprandial inflammation and SCI. This knowledge will support the idea of controlling
circulating HA and neutralizing MARCO to combat SCI and related diseases.

## Key facts

- **NIH application ID:** 10861785
- **Project number:** 5R01DK136532-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Yi Zhu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $416,464
- **Award type:** 5
- **Project period:** 2023-06-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10861785

## Citation

> US National Institutes of Health, RePORTER application 10861785, Postprandial activation of hyaluronan-MARCO axis contributes to systemic chronic inflammation (5R01DK136532-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10861785. Licensed CC0.

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