# Zinc Finger Protein 949 as a Potential Transcriptional Suppressor of Adipocyte Hypertrophy - Resubmission - 1

> **NIH NIH R03** · NEW YORK INST OF TECHNOLOGY · 2024 · $105,723

## Abstract

Background: The cellular events that cause adipocytes to increase lipid capacity (hypertrophy) characteristic of
obesity remain largely unknown. We have discovered that mice with targeted genetic deletion of diaphanous 1in
adipose tissue are protected from diet-induced obesity and exhibit reliably elevated levels of the gene encoding
the zinc finger protein 949 (Zfp949) in both brown and white adipose tissue. There is only limited published
information regarding the physiological role of Zfp949 but what is available has identified Zfp949 as
transcriptional suppressor of embryonic development. Preliminary data from our laboratory discovered that
genetic manipulations that result in lowering the expression of Zfp949 in adipocytes causes those cells to
accumulate significantly more triglycerides than control cells throughout the differentiation process. Thus, this
novel model of adipocyte hypertrophy will allow us to identify the precise cellular changes that account for the
increased lipid accumulation in Zfp949 knock-down adipocytes. Furthermore, the proposed studies aim to
determine whether increasing the expression of Zfp949 represent a therapeutic target for the treatments and/or
prevention of obesity.
Hypothesis: In line with a common function of proteins in the zinc finger family and based on a published report
supporting this role, we hypothesize that Zfp949 functions as suppressor of genes and proteins that promote
lipid buildup in adipocytes. Furthermore, we hypothesize that adipocytes genetically altered to overexpressed
Zfp949 will be protected from adipocyte hypertrophy and therefore it may represent a potential therapeutic target
for the treatment and/or prevention of obesity and other diseases associated with excess lipid buildup.
Approach: We will leverage RNA sequencing, proteomic and lipidomic studies to perform an unbiased
assessment of the genes, proteins and lipid classes that underlie adipocyte hypertrophy and thereby gain insight
into the cellular mechanisms that promote hypertrophy. Similarly, we will also harness those tools to assess
whether or not overexpressing Zfp949 represents a potential therapeutic approach to treat obesity.
Significance: One of the limitations to being able to study the cellular processes that take place in adipocytes
during hypertrophy is that currently it is not technically feasible to isolate hypertrophied adipocytes from subjects
in vivo to be able to identify the precise cellular changes that promote lipid accumulation. Here, we provide a
new cellular model that will allow for detailed studies on the underlying cellular processes that promote adipocyte
hypertrophy in vitro. Furthermore, in light of the lack of effective treatments for obesity, the fast growing
prevalence of obesity and the fact that obesity is a risk factor for cardiovascular disease and diabetes, if is of
paramount importance to be able to identify novel therapeutic targets for obesity. The clinical significance of the
proposed...

## Key facts

- **NIH application ID:** 11203764
- **Project number:** 7R03DK138218-02
- **Recipient organization:** NEW YORK INST OF TECHNOLOGY
- **Principal Investigator:** Henry H Ruiz
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $105,723
- **Award type:** 7
- **Project period:** 2024-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11203764

## Citation

> US National Institutes of Health, RePORTER application 11203764, Zinc Finger Protein 949 as a Potential Transcriptional Suppressor of Adipocyte Hypertrophy - Resubmission - 1 (7R03DK138218-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11203764. Licensed CC0.

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