# Role of extracellular vesicles in the regulation of immunometabolism in obesity

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $347,056

## Abstract

Project Abstract/Summary
The worldwide prevalence of obesity has reached pandemic proportions. Obesity has strong inflammatory
underpinnings, which are associated with the development of chronic inflammatory diseases, including
Alzheimer’s disease (AD). However, the mechanisms by which obesity provokes aberrant inflammation are
not clearly defined.
 Obesity-induced hepatosteatosis is frequently accompanied by hepatic insulin resistance,
subsequently causing hyperinsulinemia. In our parent R01 study, we aim to demonstrate that in obesity,
hyperinsulinemia enhances the biogenesis and secretion of pro-inflammatory extracellular vesicles (EVs) and
that EVs cause aberrant inflammation. In this Administrative Supplements (NOT-AG-20-034), we propose to
investigate the pathogenesis of AD by applying our findings and experimental tools used in researching pro-
inflammatory EVs. We hypothesize that in obesity, EVs become pro-inflammatory and induces abnormal
inflammatory responses even in the brain, which contribute to the development of AD.
 As recent evidence suggests, an important role of liver function is in the pathophysiology of AD, and
so we hypothesize that H-EVs under obesity and hyperinsulinemia mediate the pathophysiology of AD. These
preliminary results led us to the hypotheses: (1) during the development of hyperinsulinemia, hepatocytes
secrete pathologic, pro-inflammatory EVs, and (2) these pro-inflammatory EVs are uptaken by cells in the
brain leading to aberrant inflammation. To test this, we will pursue the following Aims:
 Studies in this proposal will: (1) determine recipient cells of EVs in the brain and their inflammatory
status, and (2) determine the role of APOE genetic variants in the pro-inflammatory traits of EVs. This study
would be a critical step addressing these unsolved questions of how obesity and hyperinsulinemia are
associated with the development of AD and identifying potential therapeutic targets for preventing and treating
AD in humans.

## Key facts

- **NIH application ID:** 10289446
- **Project number:** 3R01DK123181-02S1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Takahisa Nakamura
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $347,056
- **Award type:** 3
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10289446

## Citation

> US National Institutes of Health, RePORTER application 10289446, Role of extracellular vesicles in the regulation of immunometabolism in obesity (3R01DK123181-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10289446. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*