# Hepatic FOXA3 Links NAFLD to Atherosclerosis

> **NIH NIH R01** · NORTHEAST OHIO MEDICAL UNIVERSITY · 2022 · $511,155

## Abstract

Project Summary
Project Summary: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases
worldwide, which includes simple steatosis (NAFL) and non-alcoholic steatohepatitis (NASH). NAFLD not only
causes liver dysfunctions but also induces extra-hepatic complications. Accumulating data indicate that
cardiovascular disease (CVD) is the major cause of deaths in NAFLD patients. So far, the mechanism underlying
the development of NAFLD is poorly understood. In addition, it is unclear why NAFLD patients have increased
incidence of CAD. Forkhead box A3 (FOXA3) is a transcription factor whose function in lipid or lipoprotein
metabolism has not been established. Our preliminary studies show that hepatic FOXA3 expression is markedly
reduced under common metabolic stress. Using over-expression or knockdown approaches, we show that
hepatic FOXA3 regulates hepatic lipid and plasma HDL levels as well as the expression of HDL-associated
proteins. These novel data suggest that dysregulation of hepatic FOXA3 may play an important role in the
pathogenesis of both NAFLD and CVD. To test this hypothesis, we will use both gain- and loss-of-function
approaches. Completion of the proposed studies may uncover a novel role of hepatic FOXA3 in the development
of NAFLD and atherosclerosis and may offer novel insights into the mechanism by which NAFLD is a risk factor
for CAD.

## Key facts

- **NIH application ID:** 10364733
- **Project number:** 5R01DK118805-04
- **Recipient organization:** NORTHEAST OHIO MEDICAL UNIVERSITY
- **Principal Investigator:** Yanqiao Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $511,155
- **Award type:** 5
- **Project period:** 2019-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364733

## Citation

> US National Institutes of Health, RePORTER application 10364733, Hepatic FOXA3 Links NAFLD to Atherosclerosis (5R01DK118805-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10364733. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*