# Epigenetic dysregulation of transposons in obesity

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $432,500

## Abstract

Project Summary/Abstract
A dramatic increase in the prevalence of obesity and related complications over the last few decades has led
to a worldwide epidemic. In the U.S. alone, approximately one in three adults over the age of 20 are obese and are
at risk for cardiovascular disease, fatty liver, type 2 diabetes and several types of cancer. Our recent work has
demonstrated that diet-induced obesity (DIO), but means of a “western” high fat and high sucrose diet lead to
persistent epigenetic modifications in the liver, thereby mediating pervasive changes in transcriptional regulatory
programs. Notably, we identified a strong genetic component to these environmentally induced epigenetic
modifications with the sites of obesity associated epigenetic modifications being largely specific to individual strains
of mice. Strikingly, a large proportion of the epigenetic variation we observed across strains occurred at
transposable elements (TEs). These genomic elements constitute approximately half of the human and mouse
genomes and have contributed to the evolution of genomes and genomic diversity. While certain classes of TEs are
known to be active in early developmental cells, they are generally transcriptionally silenced in later stages of
development through mechanisms such as DNA methylation. There is increasing evidence, however, that TEs can
be activated somatically and that this dysregulation can contribute to altered gene regulatory programs and disease
progression. Our recent work indicates that TEs can be dysregulated in the liver under obesogenic conditions and
alter the regulation of genes important for metabolism. Despite the increasing evidence of the importance of TE
dysregulation in altering gene regulation and disease progression, the mechanisms responsible for this
dysregulation remain poorly understood. According to our hypothesis, obesogenic conditions promote the epigenetic
dysregulation of TEs through alterations in DNA methylation profiles and that this can be prevented or reversed
therapeutically. Our aims are to: 1) characterize the obesogenic conditions involved in TE dysregulation, 2)
determine the role of DNA methylation in mediating obesity associated TE dysregulation and 3) determine if TE
dysregulation can be prevented or reversed through dietary supplementation. The results generated from this
proposed work will explore a novel molecular mechanism that is associated with the progression of obesity and
related complications. These results will furthermore provide a greater understanding of how dysregulation of TEs
contribute to other diseases.

## Key facts

- **NIH application ID:** 9977151
- **Project number:** 5R01DK112041-04
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Dustin Edward Schones
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,500
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977151

## Citation

> US National Institutes of Health, RePORTER application 9977151, Epigenetic dysregulation of transposons in obesity (5R01DK112041-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977151. Licensed CC0.

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