# Elucidating alcohol-induced metabolic remodeling of critical organs

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $412,125

## Abstract

Project Summary/Abstract
We aim to comprehensively determine how alcohol consumption alters the metabolism of critical
organs, which can contribute to alcohol-induced organ damage. Alcohol consumption is the leading
cause of public health burden worldwide. Chronic alcohol consumption is tightly associated with the
development of cirrhosis, kidney dysfunction, intestinal inflammation, immune dysregulation,
neurological damage, and cancers. However, it is still incompletely understood how alcohol and its
metabolic products impact organ metabolism and potentially cause organ damage. Metabolism is a
dynamic process like a flowing river. However, conventional methods that measure static snapshots
such as gene expression, protein, or metabolite levels do not provide information about metabolic
activities. For example, increased blood glucose levels can be due to either elevated production or
reduced consumption by a dozen of organs. To resolve this issue, we will employ our unique platform,
arteriovenous (AV) metabolomics, to quantitatively measure the dynamic metabolic activities of all
organs relevant to alcoholic diseases (Aim 1). We will collect arterial blood and 10 organ-specific
venous blood from alcohol-fed subjects and measure metabolite concentration gradients using liquid-
chromatography mass spectrometry (LC-MS). This will inform how much and what kind of metabolites
are absorbed or released by each organ. For this study, we will use pigs because pigs are similar to
humans in terms of voluntary alcohol drinking behavior, addiction/intoxication phenotypes, and alcohol
metabolic rate. By measuring ~1,300 metabolites’ movements between 10 major organs in pigs after
alcohol feeding for three different durations, we will elucidate how each organ’s metabolism changes by
alcohol consumption over time. To identify genes that drive alcohol-induced organ metabolic changes,
we will also perform RNA-seq in the same pig tissues and employ new bioinformatics analysis to
integrate these two omics data (Aim 2). Dr. Marcus Seldin, a bioinformatics expert, will then perform a
battery of systematic correlation analyses using his innovative computational tools. Finally, we will
validate the top candidate gene-metabolite relationships in cultured cells using gain/loss-of-function
experiments. Such genes that mediate the alcohol-induced organ metabolism changes can be drug
targets to mitigate alcohol’s detrimental effects. Our study will thus delineate previously unrecognized
metabolic changes by alcohol in multiple organs as well as the key responsible genes, illuminating the
way for targetable therapy to prevent alcohol-induced organ metabolic remodeling.

## Key facts

- **NIH application ID:** 10667050
- **Project number:** 1R21AA030358-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Cholsoon Jang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $412,125
- **Award type:** 1
- **Project period:** 2023-09-12 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10667050

## Citation

> US National Institutes of Health, RePORTER application 10667050, Elucidating alcohol-induced metabolic remodeling of critical organs (1R21AA030358-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10667050. Licensed CC0.

---

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