# Novel mechanisms regulating adipose tissue function in health and disease

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $452,362

## Abstract

PROJECT SUMMARY/ABSTRACT
Excessive adipose tissue expansion causes obesity, a major risk factor for the development of metabolic
disease. Three types of fat cells exist -white, brown and beige- involved in maintaining the balance between
calories hoarded and those consumed. It has been recently suggested that increasing energy dissipation via the
induction of thermogenesis in brown and beige adipocytes could represent a strategy to combat metabolic
disease; however, at the present time, our understanding of the key targetable regulators involved in this process
is still limited. My laboratory has identified the heat shock factor HSF1 as a novel transcriptional regulator of
thermogenesis and has preliminary evidence demonstrating that HSF1 regulates histone demethylases, that
obesity is associated with low levels of HSF1 and that ablation of HSF1 in fat leads to metabolic dysfunction.
Based on this knowledge, we propose to determine how fat tissue is epigenetically reprogrammed in obese
states and identify new molecular mechanisms controlling adipose tissue biology through the analysis of novel
upstream regulators and downstream effectors of HSF1 in fat. The results of our studies will identify novel
regulatory mechanisms controlling adipose tissue biology and specific epigenetic signatures contradistinctive of
obese fat, identify HSF1 is a novel molecular link between extrinsic stimuli and transcriptional and epigenetic re-
programming of adipose tissue, and a possible new therapeutic target for the treatment of metabolic dysfunction.
To perform the studies outlined we will take advantage of unique fat specific HSF1- and adenosine receptor A2A
knock-out mice generated in our laboratory and of techniques and reagents generated over the years and more
innovative ones. In Aim 1 will identify novel chromatin signatures in adipose tissues associated with obesity and
will assess the role of HSF1 in the epigenetic control of adipose tissue biology and homeostasis; in Aim 2 we
will characterize novel regulators of adipocyte biology through the identification of new molecular targets of HSF1
in adipocytes, using state-of-the-art next generation sequencing technologies, in addition to candidate
approaches; in Aim 3 we will identify novel pathways regulating innate thermogenesis in fat cells.
We expect that the studies outlined will illuminate novel mechanisms that control energy balance in physiological
and pathological metabolic states and will define new approaches to increase energy dissipation and combat
metabolic disease.

## Key facts

- **NIH application ID:** 10917236
- **Project number:** 5R01DK133377-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Elisabetta Mueller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $452,362
- **Award type:** 5
- **Project period:** 2023-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917236

## Citation

> US National Institutes of Health, RePORTER application 10917236, Novel mechanisms regulating adipose tissue function in health and disease (5R01DK133377-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10917236. Licensed CC0.

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