# A Drosophila model for Alcoholic Liver Disease

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $243,656

## Abstract

Alcohol consumption can have life-threatening effects on human health; in fact, the overall disease burden
from alcohol is estimated to exceed 3% of deaths throughout the world. The consequences of alcohol are
particularly severe in the liver where alcohol is metabolized and leads to Alcoholic Liver Disease (ALD). ALD
occurs as a variety of conditions including fatty liver (steatosis), hepatitis, fibrosis, and hepatocellular
carcinoma (HCC). Other behaviors with adverse effects on health, such as smoking, often coincide with
alcohol consumption, patients under-report their consumption of alcohol, and there is substantial genetic
variation across the population; therefore, elucidating the mechanisms underlying ALD in patients presents a
number of significant challenges. To overcome these challenges in ALD research, we developed a
Drosophila (fruit fly) model of ALD using the Drosophila organ most similar to the mammalian liver, a
bipartite organ of the “fat body” and the “oenocytes.” Strikingly, the fat body significantly increases in size
(organomegaly) in larvae exposed to alcohol, reminiscent of mammalian ethanol-induced hepatomegaly.
Existing animal models for ALD have some advantages but also face certain limitations. Drosophila
recapitulate many phenomena relevant to disease, and this model system has been used effectively to model
diverse conditions from autism to cancer. Drosophila represent an ideal system to explore effects of genetic
susceptibility, including germline or somatic mutations in specific tissues, combined with environmental
exposure such as exposure to alcohol and other forms of oxidative stress. Although our Drosophila ALD model
also faces limitations, it bypasses some inherent limitations of existing animal models and brings the power of
Drosophila genetics to the study of ALD, namely (1) 10-day generation time, (2) the ease of performing a large
number of parallel genetic interaction studies, (3) the utility of descriptive phenotypic analysis, (4) the ability to
address the functional relevance of candidate molecules in physiological setting, and (5) the wealth of genetic
tools and reagents. Thus, our Drosophila ALD model provides an extremely practical, rapid, efficient, and cost-
effective system for discovery and for developing meaningful mechanistic hypotheses to then address in
vertebrate models. Establishing the Drosophila fat body and oenocytes as a model to study ALD will be a
tremendous resource and make a significant impact on the field. Flies are also an excellent in vivo system
capable of simultaneously evaluating chemical compound stability, bioavailability, toxicity, and efficacy in
modifying disease-relevance phenotypes. In summary, our Drosophila ALD model is a valuable resource that
complements existing ALD model systems to significantly advance our understanding of the etiology of ALD
and to serve as a platform for drug discovery.

## Key facts

- **NIH application ID:** 9953932
- **Project number:** 5R21AA025722-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** CATHIE M PFLEGER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $243,656
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953932

## Citation

> US National Institutes of Health, RePORTER application 9953932, A Drosophila model for Alcoholic Liver Disease (5R21AA025722-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9953932. Licensed CC0.

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