# Epigenetic regulation of adipose development and remodeling

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $618,106

## Abstract

Project Summary/Abstract
White adipose tissue has a central role in maintaining whole-body metabolic health. Thus, it is
critical to understand how adipocyte develops and how it remodels in response to high caloric
diet. Accumulating evidence indicates that epigenetics plays a critical role in orchestrating these
processes, however, the mechanisms by which it does so remain largely unknown. In the last
funding cycle, we have demonstrated how the enzymatic effectors of DNA methylation regulates
multiple aspects of adipose biology, including insulin sensitivity and WAT browning. The goal of
this proposal is to better understand how epigenetics controls adipose tissue development and
remodeling under chronic nutrition and its impact on metabolism, focusing specifically on TET3,
an active DNA demethylase. Consistent with our initial discovery finding an increased Tet3
expression during adipogenesis of naïve APCs, we noted a pro-adipogenic function for TET3
using primary APCs. Moreover, reduced WAT development was observed in mice deficient for
Tet3 in APC cells, but not Tet1- or Tet2, nor deficient for Tet3 in mature adipocytes. WAT from
Pdgfra-Tet3 KO mice on a high fat diet (HFD) had reduced adipose mass and adipocyte number,
with decreased signs of fibro-inflammation, suggesting that Tet3 deficiency prevents unhealthy
adipose expansion. Further, these KO mice on HFD dramatically improved insulin resistance and
glucose intolerance compared to WT mice. In line with these morphological and metabolic
changes in KO mice, our transcription and DNA methylation profiling studies revealed that TET3
targets a defined set of key target genes, including many genes involved in extracellular
remodeling (ECM). Based on these novel and exciting preliminary findings, we hypothesize that
TET3 is a critical epigenetic regulator of adipocyte development and remodeling by regulating
important target genes. To test our hypothesis, Aim1 will firmly establish the role of TET3 function
in adipogenesis using various Tet3 conditional knockout and lineage tracing mouse models. Aim2
will elucidate transcriptional and epigenetic basis of TET3 function by the use of transcriptomic
and epigenomic approaches. Aim 3 will investigate the TET3 targets critical for adipogenesis and
remodeling, and Aim 4 will examine the metabolic consequence of reduced adipogenesis from
Tet3 deficiency. Successful completion of the proposed studies will provide novel therapeutic
targets for metabolic disorders including obesity and type 2 diabetes.

## Key facts

- **NIH application ID:** 10803051
- **Project number:** 2R01DK116008-06A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Sona Kang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $618,106
- **Award type:** 2
- **Project period:** 2017-12-18 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803051

## Citation

> US National Institutes of Health, RePORTER application 10803051, Epigenetic regulation of adipose development and remodeling (2R01DK116008-06A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10803051. Licensed CC0.

---

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