# Role of adipocyte gene expression regulation by Zfp407 in adipocyte biology and metabolic disease

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $400,000

## Abstract

Project Summary
Adipocytes serve as the body’s primary site for lipid storage and act as signaling centers to coordinate
the physiological response to an organism’s nutritional and metabolic state. A better understand of the
molecules underlying adipocyte regulation and function will improve our knowledge of the
pathophysiology of obesity and type 2 diabetes, which are associated with altered adipocyte function.
This proposal will define the metabolic and molecular effects of a poorly understood transcription factor,
Zfp407, that was recently identified by our lab as a critical molecule for adipocyte function and insulin
sensitivity. We showed that Zfp407 deficiency has broad effects on adipocyte gene expression and
results in reduced fat mass, illustrating the critical role of Zfp407 in adipose biology. However, the
detailed physiological significance of Zfp407 and cellular mechanisms underlying them remain poorly
understood. We propose three Aims to identify the critical physiological role of Zfp407 in differentiating
and mature adipocytes and to determine the molecular mechanism by which Zfp407 controls gene
expression in adipocytes. In Specific Aim 1, we will discover the physiological function of Zfp407 in
mature adipocytes by testing whether constitutive and temporal deletion of Zfp407 in adipocytes alters
adipocyte number, survival, and function and determining the metabolic consequences under normal
and obesogenic conditions. In Specific Aim 2, we will elucidate the role and mechanism of Zfp407 in
the differentiation of white, brown, and beige adipocytes. In Specific Aim 3, we will determine the
molecular mechanism by which Zfp407 regulates the adipocyte transcriptome via PPARγ-dependent
and PPARγ-independent mechanisms by combining state-of-the-art genomic approaches such as
GRO-Seq and BRIC-Seq with classic biochemical techniques. Collectively, these studies will improve
our mechanistic understanding of how the regulation of gene expression controls adipocyte
differentiation and function. These data will improve our understanding of the pathophysiology of
metabolic disease and may identify new translational opportunities for treating obesity and type 2
diabetes.

## Key facts

- **NIH application ID:** 9980891
- **Project number:** 5R01DK119305-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** DAVID A BUCHNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $400,000
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980891

## Citation

> US National Institutes of Health, RePORTER application 9980891, Role of adipocyte gene expression regulation by Zfp407 in adipocyte biology and metabolic disease (5R01DK119305-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9980891. Licensed CC0.

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