Chronic Alcohol Consumption Disrupts the Skeletal Muscle Circadian Clock in Female Mice

Abstract

The intrinsic skeletal muscle core clock has emerged as a key feature of metabolic control and influences several aspects of muscle physiology. Acute alcohol intoxication disrupts the core molecular clock, but whether chronic consumption, like that leading to alcoholic myopathy, is also a zeitgeber for skeletal muscle remains unknown. The purpose of this work was to determine whether chronic alcohol consumption dysregulates the skeletal muscle core molecular clock and clock-controlled genes (CCGs). C57BL/6Hsd female mice (14 weeks old) were fed a control (CON) or alcohol (EtOH) containing liquid diet for 6 weeks. Gastrocnemius muscles and serum were collected from CON and EtOH mice every 4-h for 24-h. Chronic alcohol consumption disrupted genes of the core clock including suppressing the rhythmic peak of expression of Bmal1, Per1, Per2, and Cry2. Genes involved in the regulation of Bmal1 also exhibited lower rhythmic peaks including Reverb α and Myod1. The CCGs, Dbp, Lpl, Hk2, and Hadh were also suppressed by alcohol. The nuclear expression patterns of MYOD1, DBP, and REVERBα were shifted by alcohol, while no change in BMAL1 was detected. Overall, these data indicate that alcohol disrupted the skeletal muscle core clock but whether these changes in the core clock are causative or a consequence of alcoholic myopathy requires future mechanistic confirmation.

Multi‐omics analysis of alcohol effects on the liver in young and aged mice

“…This was further underlined by results from the differential expression analysis, which revealed genes known to be associated with alcohol consumption and (alcohol‐induced) liver injuries, such as Bhlhe40, 39 Klf10 , 40 and Txnip 41,42 . For some genes, such as fatty acid synthase ( Fasn ), a clear interaction between age and ethanol intake was observed.…”

Genetically mediated associations between chronotype and neuroimaging phenotypes in the UK Biobank: a Mendelian randomisation study

“…Clock gene expression is altered during the development of drug and alcohol addictions, while circadian disruptions predispose to increased addictive behavior [57]. Beyond this bi-directional relationship, in mice alcohol has been shown to disrupt peripheral skeletal circadian clocks by September 1, 2023 9/26 suppressing core clock genes regulating Bmal1, Period, and Cry genes (orthologs of their human counterparts) [58]. Individuals with generalized anxiety disorder and a morning (early) chronotype reported better sleep quality and parasympathetic emotional regulation than those with an evening preference [59].…”