# AKR1a1 as a novel therapeutic target for Non-Alcoholic Fatty Liver Disease

> **NIH NIH F30** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $53,974

## Abstract

PROJECT SUMMARY/ABSTRACT
Non-alcoholic Fatty Liver Disease (NAFLD) is characterized by hepatocyte fat accumulation in the absence of
alcoholic or viral etiologies, and is part of a spectrum of disease ranging from isolated steatosis to
hepatocellular carcinoma (HCC). NAFLD is estimated to affect nearly one-quarter of the world's population. As
the incidence of NAFLD-associated HCC has risen rapidly over the past few decades, it has become clear that
NAFLD is an emerging public health crisis for which there is currently no approved pharmacologic intervention.
This project will investigate the role of AKR1a1—a recently discovered protein denitrosylase—in the
pathogenesis of NAFLD through interrogation of its role in modulating hepatic lipid metabolism via reversible S-
nitrosylation of key lipogenic enzymes. Further, the potential for AKR1a1 as a novel therapeutic target to
prevent NAFLD will be investigated. To this end, the study will employ a variety of techniques including:
CRISPR-Cas9 genome editing and administration of small molecule inhibitors in dietary models of murine
NAFLD; isotope tracing studies to interrogate whole-pathway and enzyme-specific effects on lipid metabolism;
resin-assisted capture to assess endogenous S-nitrosylation of enzymes; and site-directed mutagenesis to
determine the functional role of S-nitrosylation. Together, this study will provide novel insight into the regulation
of hepatic lipid metabolism and the pathophysiology of NAFLD, and identify potential therapeutic targets.

## Key facts

- **NIH application ID:** 10771967
- **Project number:** 5F30DK128944-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Nicholas Venetos
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2022-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10771967

## Citation

> US National Institutes of Health, RePORTER application 10771967, AKR1a1 as a novel therapeutic target for Non-Alcoholic Fatty Liver Disease (5F30DK128944-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10771967. Licensed CC0.

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