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

> **NIH NIH R03** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $10,000

## Abstract

PROJECT SUMMARY
Background: The cellular events that cause adipocytes to accumulate excessive amounts of triglycerides
(hypertrophy), a key characteristic of obesity, remain largely unknown. We have discovered that mice with
targeted genetic deletion of adipose tissue diaphanous 1 are protected from diet-induced obesity and exhibit
reliably higher expression of the gene zinc finger protein 949 (Zfp949) in both brown and white adipose tissues.
The literature on the physiological role of Zfp949 is limited to its roles as a transcriptional suppressor of embryonic
development. Preliminary data from our laboratory demonstrate that lowering the expression of Zfp949 in
adipocytes prevents triglycerides accumulation when exposed to excess fatty acids. Thus, this novel model of
adipocyte hypertrophy will allow us to identify the genes, protein and lipids that contribute to adipocyte obesity.
Furthermore, the proposed studies aim to determine whether overexpression of Zfp949 represents 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 suppresses genes and proteins that promote lipid accumulation
in adipocytes and thus, overexpression will be protective from fatty acid-induced hypertrophy.
Approach: We will leverage RNA sequencing, proteomic and lipidomic studies for unbiased assessment of the
genes, proteins and lipids that underlie adipocyte hypertrophy. This multi-omic approach will identify the cellular
processes that promote lipid accumulation in adipocytes. 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 it is not possible to isolate hypertrophied adipocytes from subjects in vivo thus
hindering our full understanding of the causes of obesity. The innovative question and cellular model will allow
us to unveil the underlying cellular processes that cause adiposity and obesity. In light of the lack of effective
and safe treatments for obesity, the fast growing prevalence of this disease, and its link as a major risk factor for
cardiovascular disease and diabetes, if is of paramount importance to better understand the cellular processes
underlying obesity, which the proposed studies aim to address. The clinical significance rests on the notion that
the results of the proposed studies will identify key genes, proteins and metabolic pathways that promote lipid
accumulation in adipocytes as well as identify the specific lipid species that contribute to adipocyte hypertrophy,
which via established collaborations, can then be validated in future proposals in samples from obese human
subjects and may be targeted as potential therapeutic cand...

## Key facts

- **NIH application ID:** 10987761
- **Project number:** 1R03DK138218-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Henry H Ruiz
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $10,000
- **Award type:** 1
- **Project period:** 2024-07-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987761

## Citation

> US National Institutes of Health, RePORTER application 10987761, Zinc Finger Protein 949 as a Potential Transcriptional Suppressor of Adipocyte Hypertrophy - Resubmission - 1 (1R03DK138218-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10987761. Licensed CC0.

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