# The role of muscle-derived extracellular vesicles in adipocyte metabolism

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA LINCOLN · 2021 · $144,460

## Abstract

Extracellular vesicles (EVs) are membrane-bound vesicles released by virtually all cell types, potentially 
mediating intercellular communication and thereby play essential roles in many physiological and pathological 
processes. This capacity relies on EVs’ ability to serve as delivery vehicles for a wide range of endogenous 
cargo molecules, such as RNAs, proteins, and lipids. EVs have also been found to display tissue-specific 
recognition mediated by surface molecules (such as integrins and glycans), making them promising for drug 
delivery applications. However, a better understanding of EV composition and cargo is necessary to enable the 
use of EVs as delivery vehicles. Preliminary data demonstrate that after a hypertrophic stimulus, muscle-derived 
EVs (mEVs) are specifically delivered to adipose tissue. Interestingly, the delivery of mEVs to adipose tissue 
induced lipolysis and fat loss in high-fat-diet-fed mice. This exciting preliminary data could represent the first 
steps into the development of therapy for obesity. Additionally, our preliminary data indicate high levels of 
diacylglycerol (DAG) within mEVs, which could, upon delivery, mediate protein kinase C (PKC) activation and 
induce changes in adipocyte metabolism. The proposed project expands upon our preliminary data and is based 
on the overarching hypothesis that a hypertrophic stimulus would change the lipid makeup of mEVs, leading to 
adipocyte metabolism changes. More specifically, it is hypothesized that a hypertrophic stimulus will increase 
DAG concentration within mEVs that will induce adipocyte lipolysis through PKC activation, resulting in wholebody 
metabolic benefits. In order to confirm our preliminary data, we will use muscle cells (C2C12 cells) to 
isolate mEVs with or without a hypertrophic stimulus (treatment with insulin-like growth factor 1) and perform a 
lipid profile of these vesicles. After establishing the lipid profile, mEVs will be transferred to adipocyte cells 
(3T3L1 cells) or will be tail vein injected into obese mice. The purpose of this project is to test this working 
hypothesis by pursuing three specific aims. Specific Aim 1 is to determine whether the lipid composition of 
skeletal muscle extracellular vesicles is altered in response to a hypertrophic stimulus; Specific Aim 2 is to 
determine whether mEVs stimulate adipocyte lipolysis through PKC activation; and Specific Aim 3 is to 
determine whether extracellular vesicles in response to a hypertrophic stimulus can induce fat loss through 
enhanced lipolysis in obese mice. Preliminary data suggest that mEVs provide beneficial effects on adipocyte 
metabolism and induce fat loss in obese mice. If the results of the proposed experiments provide evidence to 
support the hypothesis, a future R01 application will seek to rigorously test which class/classes of lipids can 
specifically mediate changes in adipocyte metabolism.

## Key facts

- **NIH application ID:** 10263209
- **Project number:** 5P20GM104320-08
- **Recipient organization:** UNIVERSITY OF NEBRASKA LINCOLN
- **Principal Investigator:** Ivan J Vechetti
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $144,460
- **Award type:** 5
- **Project period:** 2014-08-05 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10263209

## Citation

> US National Institutes of Health, RePORTER application 10263209, The role of muscle-derived extracellular vesicles in adipocyte metabolism (5P20GM104320-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10263209. Licensed CC0.

---

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