# Coordinate Regulation of an Alcohol Protective Response by the Liver-derived Hormone FGF21

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $368,906

## Abstract

Project Summary
Alcohol abuse and related diseases exact a staggering health and economic toll, and thus there is a dire
need for novel therapeutic approaches. The hormone FGF21, which is rapidly and robustly induced in liver
in response to ethanol exposure, is an exciting new pharmaceutical candidate. FGF21 acts on the brain to
suppress alcohol consumption and to stimulate water drinking. In this application, we propose that FGF21
mediates these protective effects by acting directly on neurons expressing the neuropeptide, neurotensin,
which is a well-established regulator of ethanol and water intake. We further propose that liver-derived
FGF21 also protects against ethanol-induced hypothermia and liver injury by activating the sympathetic
nervous system and stimulating thermogenesis in brown adipose tissue. We will test these hypotheses in a
series of experiments that employ our unique collection of genetically-engineered mouse models, including
mice selectively lacking FGF21’s obligate co-receptor -Klotho in neurotensin neurons. We anticipate that
these studies will provide important insights into the tissues and underlying mechanisms whereby FGF21
protects against ethanol-induced toxicity. Moreover, since FGF21 is already in clinical trials for metabolic
disease-related indications, these studies will aid in determining whether FGF21 can be repurposed
pharmaceutically for treating alcohol abuse and its associated pathologies.

## Key facts

- **NIH application ID:** 10236301
- **Project number:** 5R01AA028473-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Steven Kliewer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $368,906
- **Award type:** 5
- **Project period:** 2020-08-10 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236301

## Citation

> US National Institutes of Health, RePORTER application 10236301, Coordinate Regulation of an Alcohol Protective Response by the Liver-derived Hormone FGF21 (5R01AA028473-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10236301. Licensed CC0.

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