# DNA Methylation and Vascular Function in Obesity: Role of Exercise and Weight Loss

> **NIH NIH R00** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $245,800

## Abstract

PROJECT SUMMARY/ABSTRACT
The long-term goal of this study is to identify valid targets and strategies for the prevention and treatment of
obesity-related cardiovascular disease. Obesity is characterized by a large accumulation of fat tissues that
secrete numerous inflammatory mediators (called adipocytokines), generating a systemic inflammatory state.
These adipocytokines induce vascular dysfunction which is the initial step towards developing cardiovascular
disease. Obesity is affected by environmental factors such as diet and physical activity. These factors induce
epigenetic changes, which are changes that affect gene expression without altering the DNA sequence. One of
these epigenetic modifications is the reduction in DNA methylation (referred to as hypomethylation) resulting in
subsequent increases in gene expression. Our preliminary studies showed that the extracted DNA from fat
tissues of obese subjects is hypomethylated compared to non-obese controls. DNA hypomethylation correlated
significantly with higher expression of adipocytokines and impaired vasodilation in obese subjects. Therefore,
we hypothesize that the increase in adipocytokine expression in obese adults is mediated by DNA
hypomethylation and that DNA hypomethylation is a promising target to prevent obesity-associated inflammation
and vascular dysfunction. The flexible modifiable nature of DNA methylation makes it a perfect target for life style
interventions such as physical activity and weigh loss. Thus, we propose that aerobic exercise training and weight
loss following Bariatric surgery will reverse DNA hypomethylation and improve vascular function in obese
subjects. We will test our hypotheses by (1) Investigating abnormal DNA methylation patterns of adipocytokines
in fat tissues from obese adults between the age of 18 and 50 compared to non-obese subjects; (2) Test the
effectiveness of 12-week aerobic exercise training on reversing DNA hypomethylation and improving vascular
function in obese adults; and (3) Examine the effectiveness of weight loss surgery on DNA methylation and
vascular function. The proposed studies will improve our understanding of the epigenetic underpinning of
obesity-related vascular dysfunction, identify novel therapeutic targets for improving vascular function in obese
adults, and provide an evidence for the positive effects of aerobic exercise training and weight loss on the
prevention and treatment of obesity-associated cardiovascular disease. These studies will have a positive impact
on improving the prevention and therapeutic management of obesity-related cardiovascular morbidities that
affect millions of people worldwide. Therefore, we propose a focused career development training plan during
which the applicant will be trained in the responsible conduct of clinical research, learn all aspects of how to
start, implement and manage a clinical study and how to lead a clinical research team, efficiently. By completing
the proposed training (K99...

## Key facts

- **NIH application ID:** 9991898
- **Project number:** 5R00HL140049-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Abeer M Mohamed
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $245,800
- **Award type:** 5
- **Project period:** 2019-01-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991898

## Citation

> US National Institutes of Health, RePORTER application 9991898, DNA Methylation and Vascular Function in Obesity: Role of Exercise and Weight Loss (5R00HL140049-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9991898. Licensed CC0.

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