# Nuclear Repressors in Genomic Control of Healthful Obesity

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $420,683

## Abstract

PROJECT SUMMARY
Non-alcoholic fatty liver disease (NAFLD) afflicts nearly a quarter of Americans and is projected to become the
leading cause of end-stage liver disease in the next decade. It is driven by overnutrition, disproportionately occurs
in men, and is linked to derangements in liver lipid and sterol metabolism. The molecular determinants that
control NAFLD and its sex-bias are incompletely understood. Using conditional genetic engineering, we have
identified a profound role for the transcription factor B cell lymphoma 6 (BCL6) to direct sexually dimorphic
transcription in hepatocytes. Herein, we propose to comprehensively dissect the transcriptional regulatory
mechanisms of BCL6 underlying its sex-specific programming and the functional implications of hepatocyte Bcl6
on fatty liver disease and whole body metabolism. In Aim 1, we will test the impact of BCL6 on chromatin looping
and histone modification, its sex-specific modes of recruitment to chromatin, and coregulation with estrogen
receptor alpha. In Aim 2, we define the functional role of Bcl6 in the sexual dimorphism of NAFLD, its signaling
through bile acid pathways, and its impact on fibrosis using loss- and gain-of-function studies in vivo. Together,
these studies will reveal new molecular insights into the regulation of sexually dimorphic transcription and
NAFLD.

## Key facts

- **NIH application ID:** 10896181
- **Project number:** 5R01DK108987-09
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Grant D Barish
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $420,683
- **Award type:** 5
- **Project period:** 2016-05-10 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896181

## Citation

> US National Institutes of Health, RePORTER application 10896181, Nuclear Repressors in Genomic Control of Healthful Obesity (5R01DK108987-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10896181. Licensed CC0.

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