# Profiling extracellular vesicle cargo in obesity and type 2 diabetes

> **NIH NIH R01** · TRANSLATIONAL GENOMICS RESEARCH INST · 2020 · $722,401

## Abstract

PROJECT SUMMARY/ABSTRACT
Obesity
diabetes
adipose
spectrum
Emerging
is linked with heightened risk of insulin resistance and type 2
(T2D) Obesity is also associated attributed primarily to visceral
tissue (VAT), which increases T2D risk; however, the precise molecular mechanisms underlying the
inflammatory and metabolic mediators of dysglycemia in obesity remain poorly
studies support a role for extracellular vesicles (EVs) in both T2D and obesity.
metabolic
abnormalities,
including
. with chronic low-grade inflammation,
of understood.
EVs are a
heterogeneous class of membrane vesicles that participate in cell-cell communication through exchange of
proteins, lipids, and nucleic acids. Circulating and adipocyte-derived EVs have been shown to increase in
obesity, decrease following weight reduction, and correlate with restoration of glycemic control in T2D patients
following bariatric surgery. Adipose-derived EVs may also mediate T2D pathogenesis. We hypothesize that
protein and RNA cargo of circulating EVs contribute to metabolic derangements in obesity, and
correspondingly, to improvements in glucose metabolism associated with bariatric surgery. To address this
hypothesis, we propose a strategy to identify EV-derived protein and RNA profiles associated with obesity-
related T2D. In Aim 1, we will
derived
transcripts
assess protein and RNA (lncRNA, miRNA, and mRNA) content in plasma-
EVs obtained from T2D (N=60) and normoglycemic (N=60) individuals with obesity. Proteins and
showing T2D-associated patterns will be analyzed in an independent study sample (N=120).
Completion of this aim will result in the identification and validation of protein and RNA profiles associated with
T2D in extreme obesity. In Aim 2, we propose to determine whether T2D-associated protein and RNA
signatures emanate from VAT by evaluating cargo (protein and RNA) isolated from immuno-selected fractions
of EVs and from EVs obtained from VAT-conditioned media. Determining
involved we will establish
whether T2D-associated signatures are lost in patients who experience T2D remission following bariatric
surgery, but retained in those who remain diabetic, even in the presence of significant weight loss. In specific,
we will measure T2D-associated protein and RNA profiles identified and validated in Aim 1 in individuals who
whether VAT is the
in the pathogenesis of T2D will provide a cellular target for further studies. In Aim 3,
source
of
EVs
experience T2D remission and those who remain diabetic. Completion of this
understanding The combination of
plasma and VAT samples from bariatric surgery patients and state-of-the-art molecular characterization
provides a unique opportunity to identify those patients likely to receive the greatest benefit from bariatric
surgery, improve our understanding of T2D pathogenesis, and perhaps lead to the development of drugs that
mimic effects of surgery.
of
the
mechanisms
underlying
T2D
remission
following
aim is expected to enhance our
bariatric ...

## Key facts

- **NIH application ID:** 10018896
- **Project number:** 5R01DK120890-02
- **Recipient organization:** TRANSLATIONAL GENOMICS RESEARCH INST
- **Principal Investigator:** Johanna K DiStefano
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $722,401
- **Award type:** 5
- **Project period:** 2019-09-20 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018896

## Citation

> US National Institutes of Health, RePORTER application 10018896, Profiling extracellular vesicle cargo in obesity and type 2 diabetes (5R01DK120890-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10018896. Licensed CC0.

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