# Macrophage Trafficking, Inflammation & Metabolism in Adipose Tissue in High Fat Feeding: Role of AGE/RAGE/DIAPH1

> **NIH NIH P01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $438,405

## Abstract

The problems of obesity and insulin resistance have been linked to type 2 diabetes. Diabetes is on the rise and
fully effective treatments are lacking. In the spectrum from obesity and insulin resistance, to diabetes, profound
metabolic dysfunction is linked to increased risk for cardiovascular disease. In this Program Project, our goal is
to uncover fundamental mechanisms by which macrophage inflammation impacts metabolic dysfunction in
diabetic atherosclerosis and obesity. Published and preliminary data reveal that in high fat feeding and obesity
in human subjects and in mice, ligands of the receptor for AGE (RAGE) are increased in adipose tissue and
other key metabolic tissues, even in the absence of diabetes. Our data reveal that genetic deletion of Ager
(gene encoding RAGE) results in significant protection against high fat feeding induced obesity and insulin
resistance. Importantly, the accumulation and inflammatory polarization of adipose tissue macrophages are
greatly reduced by deletion of Ager. Project 3 will address the hypothesis that RAGE/DIAPH1 regulates
obesity, adiposity and metabolic dysfunction in high fat feeding, both via cell autonomous mechanisms, and via
macrophage cross-talk with the adipocyte. Our Project will explore four key properties of macrophage
inflammation to discover RAGE-dependent mechanisms in high fat feeding: monocyte recruitment;
macrophage retention and egress; polarization; and metabolic regulation. Project 3 will work closely with
Projects 1 and 2 to address the common vs. distinct mechanisms of macrophage inflammation in diabetic
atherosclerosis and in obesity. Project 3 will work closely with Project 1 to test novel small molecule
antagonists of RAGE/DIAPH1 interaction in atherosclerosis and in high fat feeding, and will work closely with
Project 2 to discern common vs. distinct mechanisms by which RAGE/DIAPH1 contribute to regulation of
NETRIN1/UNC5B and metabolic dysfunction in macrophages in high fat feeding. Project 3 will utilize all three
Cores of the Program over all five years.

## Key facts

- **NIH application ID:** 10150068
- **Project number:** 5P01HL131481-05
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** ANN MARIE SCHMIDT
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $438,405
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150068

## Citation

> US National Institutes of Health, RePORTER application 10150068, Macrophage Trafficking, Inflammation & Metabolism in Adipose Tissue in High Fat Feeding: Role of AGE/RAGE/DIAPH1 (5P01HL131481-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10150068. Licensed CC0.

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