# Elucidating the Transcriptional Brakes on Adipocyte Thermogenesis

> **NIH NIH F30** · DUKE UNIVERSITY · 2024 · $53,974

## Abstract

PROJECT ABSTRACT/SUMMARY
 The ability of brown adipose tissue (BAT) to expend energy through a process called adaptive
thermogenesis makes it an attractive target for intervention in obesity; however, the observation that BAT mass
diminishes in human obesity raises concerns about its ability to clinically impact body weight when fully activated.
Energy-storing white adipose tissue (WAT) can also adopt a “brown-like” thermogenic phenotype; however, there
are potent molecular brakes on thermogenic gene program in white adipocytes that help maintain its energy-
storing phenotype. Since WAT is present in far greater mass than BAT, activation of the thermogenic gene
program in white adipocytes may be a more viable strategy for intervention in obesity; however, the mechanisms
controlling the establishment and maintenance of the energy-burning vs. energy-storing adipocyte lineages
remain undefined.
 ZFP423, a member of the C2H2 family of zinc finger proteins, is a physiologically regulated transcription
factor that functions to maintain the energy-storing white adipocyte phenotype by suppressing the thermogenic
gene program characteristic of brown/beige fat cells. ZFP423 physically interacts with the brown adipocyte
determination factor, EBF2, in white adipocytes to prevent EBF2-dependent chromatin remodeling and PPARg
occupancy at key thermogenic genes.
 The experiments that I propose to conduct as part of my PhD training in the Duke University Medical
Scientist Training Program will utilize advanced approaches in biochemistry, molecular biology, and mouse
genetics. This work, conducted under the mentorship of Dr. Rana Gupta at the Duke Molecular Physiology
Institute, is designed to 1) address the hypothesis that the ability of ZFP423 to directly recruit the NuRD complex
to EBF2 is essential for its ability to suppress thermogenesis in white adipocytes (Aim1), and 2) test the
hypothesis that genetic disruption of the ZFP423-EBF complex in mice is sufficient to permit thermogenic WAT
remodeling and prevent the development of obesity and metabolic dysfunction. The overall goal of my proposed
research is to further define the critical protein-protein interactions leading to the suppression of the thermogenic
gene program by ZFP423 in white adipocytes. Successful completion of this work will highlight the importance
of transcriptional “brakes” on thermogenic gene expression in adipocytes and may suggest a strategy to unlock
the thermogenic capacity of WAT to promote weight loss and/or improve nutrient homeostasis.

## Key facts

- **NIH application ID:** 10930808
- **Project number:** 5F30DK136168-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Ashley T Truong
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2023-04-06 → 2028-04-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930808

## Citation

> US National Institutes of Health, RePORTER application 10930808, Elucidating the Transcriptional Brakes on Adipocyte Thermogenesis (5F30DK136168-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10930808. Licensed CC0.

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