# Endocrine Regulation of Alcohol Intake

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $437,190

## Abstract

PROJECT SUMMARY / ABSTRACT
In the United States, alcohol use disorder (AUD) affects ~15% of adults with the prevalence of binge drinking
on the rise in adolescents and young adults. AUD represents a major issue to healthcare given that chronic
excessive alcohol consumption in humans is associated with cardiovascular disease, metabolic syndrome, and
cancer while acute alcohol intoxication can prove lethal. Economically, AUD represents a massive burden due
to loss of productivity and associated healthcare costs. Recently, the endocrine hormone fibroblast growth
factor 21 (FGF21), known for its potent metabolic effects, was found to significantly reduce alcohol
consumption via signaling through its obligate co-receptor, β-klotho, in the brain. Importantly, single nucleotide
polymorphisms (SNPs) in both the FGF21 and β-klotho genomic loci are highly associated with increased
alcohol consumption in humans. Our preliminary data demonstrates that FGF21 treatment markedly
suppresses alcohol consumption in mice previous subjected to chronic alcohol exposure. Furthermore,
excessive alcohol consumption promotes FGF21 secretion from the liver representing a homeostatic feedback
loop to regulate alcohol consumption. However, the mechanism of FGF21 action in the brain and the neuronal
target(s) for these effects has not been determined. The overall goal of this proposal is to identify the neural
circuit(s) regulating FGF21-mediated suppression of alcohol intake. The aims of this grant are to 1) determine
the direct neuronal target(s) of FGF21 in the CNS mediating inhibition of alcohol intake, and 2) determine how
FGF21 modulates reward circuits to regulate alcohol intake and preference. To accomplish these aims, we
have generated novel animal models and tools to examine these experimental aims. These studies will provide
new fundamental insights into the regulation of alcohol intake by peripheral endocrine signals acting on the
central nervous system. In addition, these studies may identify novel therapeutic targets for the treatment of
AUD.

## Key facts

- **NIH application ID:** 10764211
- **Project number:** 5R01AA027654-05
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Matthew Joseph Potthoff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $437,190
- **Award type:** 5
- **Project period:** 2020-01-10 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764211

## Citation

> US National Institutes of Health, RePORTER application 10764211, Endocrine Regulation of Alcohol Intake (5R01AA027654-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10764211. Licensed CC0.

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