# Adipose tissue macrophages secrete exosome-miRs as paracrine/endocrine molecules to directly modulate insulin target cell function in response to obesity

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $247,460

## Abstract

Project abstract
Obesity is now an epidemic and has become one of the most common causes of
insulin resistance. Insulin resistance is the key etiology for the pathogenesis of
metabolic syndrome. Prolonged status of metabolic syndrome drives the
development of type 2 diabetes mellitus. An important event in this process is the
recruitment and activation of macrophages to the insulin target tissues. However,
the mechanisms whereby macrophages regulate the development of
obesity-induced insulin resistance are not fully understood. Obesity drives
the activation of adipose tissue macrophages (ATM) towards proinflammatory
phenotype, which subsequently affects the interaction of macrophages with
adipocytes or other insulin target cells. Here, we aim to discover exosomal
miRNA-mediated mechanisms underlying the pathogenesis of systemic insulin
sensitivity. My preliminary data show that the distinct activations of ATMs signal a
switch in profile of exosomal miRNAs that can be delivered into the insulin target
cells and exert profound regulation on insulin responses of these cells. In vivo
results indicate that transferring obese ATM-secreted exosomes impair glucose
tolerance and insulin sensitivity of lean WT recipient mice, while lean ATM
exosomes remarkably attenuate insulin resistance of obese WT recipient mice.
Therefore, I propose that adipose tissue macrophages secrete exosomal
miRNAs as paracrine/endocrine molecules controlling cellular insulin
responses of target cells, which eventually mediate systemic insulin
sensitivity. To testify this hypothesis, I will 1) investigate the regulation of
ATM-derived exosomal miRNAs on cellular insulin actions; 2) investigate the
importance of exosomal miR-155 in regulating the insulin responses; 3) determine
the mechanisms by which ATM-exosomal miRNAs regulate the cellular insulin
responses. This research will elucidate ATM-secreted exosomal miRNA-mediated
mechanisms controlling insulin sensitivity, with the ultimate goal of identifying
novel targets for therapeutic treatment of insulin resistance and type 2 diabetes.

## Key facts

- **NIH application ID:** 10242234
- **Project number:** 5R00DK115998-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Wei Ying
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $247,460
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242234

## Citation

> US National Institutes of Health, RePORTER application 10242234, Adipose tissue macrophages secrete exosome-miRs as paracrine/endocrine molecules to directly modulate insulin target cell function in response to obesity (5R00DK115998-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242234. Licensed CC0.

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