# Alcohol and the skeletal muscle clock

> **NIH NIH R21** · FLORIDA STATE UNIVERSITY · 2024 · $234,665

## Abstract

Project Summary/Abstract
Alcohol is a well-known myotoxin that with sustained use can culminate in alcohol-associated muscle disease
(AAMD), characterized by muscle weakness and functional decline, along with metabolic impairments and
decreases in muscle size (i.e., mass), that culminate in reduced quality of life. While mechanisms regulating
protein balance have previously been implicated in AAMD development, additional pathways require
exploration to develop new therapeutic targets as none currently exist. Our previous work indicates that both
binge and chronic alcohol intoxication disrupt the core molecular clock within the skeletal muscle however,
whether clock disruption contributes to the etiology of AAMD remains unknown. Overall, the long-term goal is
to mechanistically determine whether alcohol’s influence on the skeletal muscle core clock impacts alcohol-
associated disease risk, as well as to determine how alcohol modulates the core clock so that targeting of
specific clock components can be used as therapeutic interventions. Specifically, skeletal muscle contractile
strength is reduced by chronic alcohol use in a manner that closely parallels that caused by skeletal muscle-
specific core molecular clock disruption (in the absence of alcohol), inferring that alcohol-induced disruption in
the core clock may be responsible for AAMD associated weakness. Therefore, Specific Aim 1 of the current
proposal is to determine whether disruption to the skeletal muscle core molecular clock contributes to the
decreases in contractile function caused by chronic alcohol use. The second Aim will be to determine how
alcohol consumption causes skeletal muscle core clock disruption so that preventative interventions can be
developed. Specific Aim 1 will use a mouse model of muscle-specific circadian pathway dysfunction caused by
the inducible deletion of the core clock gene Brain muscle arnt like-1 (Bmal1) to determine the role of the
skeletal muscle clock on contractile function during alcohol intoxication. Specific Aim 2 will define the role of
alcohol and alcohol-related factors in the disruption of the skeletal muscle clock by investigating the influence
of both peripheral circulating factors produced during alcohol metabolism and the role of the central (i.e. brain-
specific) administration of alcohol on the circadian function within the skeletal muscle. These research
questions will be addressed by using a variety of physiological models paired with in vitro, in vivo and in situ
techniques. This investigation will be the first of its kind in the study of the effects of alcohol on core clock
function in the muscle and one of the few to consider the influence of peripheral tissues in the development of
AAMD. Lastly, it will lay the foundation for continued mechanistic investigations to determine the role of the
core molecular clock in AAMD.

## Key facts

- **NIH application ID:** 11058231
- **Project number:** 1R21AA031567-01A1
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Jennifer Lynn Steiner
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $234,665
- **Award type:** 1
- **Project period:** 2024-09-17 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11058231

## Citation

> US National Institutes of Health, RePORTER application 11058231, Alcohol and the skeletal muscle clock (1R21AA031567-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11058231. Licensed CC0.

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