Acute binge alcohol alters whole body metabolism and the time-dependent expression of skeletal muscle-specific metabolic markers for multiple days in mice

Tice, Abigail L.; Laudato, Joseph A.; Fadool, James M.; Gordon, Bradley S.; Steiner, Jennifer L.

doi:10.1152/ajpendo.00026.2022

Cited by 12 publications

(9 citation statements)

References 48 publications

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“…These changes were associated with increased circulating corticosterone levels and dysregulation of energy substrate metabolism. 57 C2C12 myoblasts treated with 100 mM of alcohol showed increased proteolysis. An inhibitor of autophagy (3-methyladenine) prevented the increase in proteolysis while a proteasome inhibitor (MG132) did not affect proteolysis, highlighting the relevance of activation of autophagic-lysosomal pathway to alcohol-induced catabolic responses in SKM.…”

Section: Results Of the Reviewed Studiesmentioning

confidence: 93%

Alcohol and Skeletal Muscle in Health and Disease

Simon

2023

ARCR

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PURPOSE Alcohol-related myopathy is one of the earliest alcohol-associated pathological tissue changes that is progressively exacerbated by cumulative long-term alcohol misuse. Acute and chronic alcohol use leads to changes in skeletal muscle mass and function. As discussed in this evidence-based review, alcohol-mediated mechanisms are multifactorial with effects on anabolic and catabolic signaling, mitochondrial bioenergetics, extracellular matrix remodeling, and epigenomic alterations. However, systematic studies are limited, especially regarding the acute effects of alcohol on skeletal muscle. SEARCH METHODS This review focuses on peer-reviewed manuscripts published between January 2012 and November 2022 using the search terms “alcohol” or “ethanol” and “skeletal muscle” in MEDLINE, PubMed, and Web of Science using EndNote reference management software. SEARCH RESULTS Eligible manuscripts included full-length research papers that discussed acute and chronic effects of alcohol on skeletal muscle mass and function in both clinical and preclinical studies. The review also includes alcohol-mediated skeletal muscle effects in the context of comorbidities. The three databases together yielded 708 manuscripts. Of these, the authors excluded from this review 548 papers that did not have “alcohol” or “muscle” in the title and 64 papers that were duplicates or did not discuss skeletal muscle. Thus, of all the manuscripts considered for this review, 96 are included and 612 are excluded. Additionally, relevant papers published earlier than 2012 are included to provide context to the review. DISCUSSION AND CONCLUSIONS Both acute and chronic alcohol use decrease protein synthesis and increase protein degradation. Alcohol also impairs mitochondrial function and extracellular matrix remodeling. However, there is a gap in the literature on the known alcohol-mediated mechanisms, including senescence, role of immune activation, and interorgan communication, on the development of alcohol-related myopathy. With increased life expectancy, changing alcohol use patterns, and increasing frequency of alcohol use among females, current observational studies are needed on the prevalence of alcohol-related myopathy. Additionally, the compounding effects of acute and chronic alcohol use on skeletal muscle with aging or exercise, in response to injury or disuse, and in the context of comorbidities including diabetes and human immunodeficiency virus (HIV), call for further investigation. Though evidence suggests that abstinence or reducing alcohol use can improve muscle mass and function, they are not restored to normal levels. Hence, understanding the pathophysiological mechanisms can help in the design of therapeutic strategies to improve skeletal muscle health.

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Section: Results Of the Reviewed Studiesmentioning

confidence: 93%

Alcohol and Skeletal Muscle in Health and Disease

Simon

2023

ARCR

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“…However, in mice, an acute dose of ethanol (binge dose) increases atrogin-1 mRNA, but no Murf-1 mRNA [ 91 ]. A study on female mice showed that 0–24 h after an acute binge, atrogin-1 , and Murf-1 mRNA results elevated, but 24–48 h post-binge Murf-1 mRNA levels decreased [ 92 ]. On the other hand, chronic ethanol increased atrogin-1 and Murf-1 gene expression, which came before skeletal muscle atrophy and then returned to baseline levels when atrophy was established [ 93 , 94 ].…”

Section: Discussionmentioning

confidence: 99%

Episodic Binge-like Ethanol Reduces Skeletal Muscle Strength Associated with Atrophy, Fibrosis, and Inflammation in Young Rats

Cáceres-Ayala

Mira

Acuña

et al. 2023

IJMS

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Binge Drinking (BD) corresponds to episodes of ingestion of large amounts of ethanol in a short time, typically ≤2 h. BD occurs across all populations, but young and sports-related people are especially vulnerable. However, the short- and long-term effects of episodic BD on skeletal muscle function have been poorly explored. Young rats were randomized into two groups: control and episodic Binge-Like ethanol protocol (BEP) (ethanol 3 g/kg IP, 4 episodes of 2-days ON-2-days OFF paradigm). Muscle function was evaluated two weeks after the last BEP episode. We found that rats exposed to BEP presented decreased muscle strength and increased fatigability, compared with control animals. Furthermore, we observed that skeletal muscle from rats exposed to BEP presented muscle atrophy, evidenced by reduced fiber size and increased expression of atrophic genes. We also observed that BEP induced fibrotic and inflammation markers, accompanied by mislocalization of nNOSµ and high levels of protein nitration. Our findings suggest that episodic binge-like ethanol exposure alters contractile capacity and increases fatigue by mechanisms involving atrophy, fibrosis, and inflammation, which remain for at least two weeks after ethanol clearance. These pathological features are common to several neuromuscular diseases and might affect muscle performance and health in the long term.

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“…This method serves as alcohol consumption “prior” to tumor inoculation. Alcohol feeding for 6 weeks or less has previously been shown to reduce protein synthetic rates and induce muscle atrophy in rodents as well as induce significant alcohol associated liver injury (Cohen et al, 2010; Mandrekar et al, 2011; Nath et al, 2011; Preedy et al, 2001; Tice et al, 2022; Thapaliya et al, 2014). Throughout the feeding protocol, all mice were given ad libitum access to 25 mL of the appropriate, freshly prepared liquid diet each day.…”

Section: Methodsmentioning

confidence: 99%

“…The gastrocnemius was powdered in liquid nitrogen and 20 mg was homogenized in TRI reagent (Zymo Research). RNA was isolated, cDNA synthesized, and RT-PCR performed as previously described using primer sequences for Murf1 and Mafbx as listed in Tice et al (2021Tice et al ( , 2022.…”

Section: Rna Extraction Cdna Synthesis and Rt-pcrmentioning

confidence: 99%

Impact of prior alcohol use on the subsequent development of cancer cachexia in male and female mice

Laudato

Tice

Johnson

et al. 2023

Alcohol: Clinical and Experimental Research

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Background Alcohol is a carcinogen and its intake prior to developing cancer and throughout its duration exacerbates cancer cachexia in rodent models. However, the effects on cancer cachexia of stopping alcohol prior to tumor establishment are unknown. Methods Male and female mice consumed either a nonalcohol control liquid diet (CON) or a 20% ethanol (kcal/day) liquid diet (EtOH) for 6 weeks. All mice then consumed a control diet and mice in the cancer groups were inoculated with C26 colon cancer cells. Gastrocnemius muscles were collected and analyzed after ~2 weeks. Results Skeletal muscle weight and male epididymal and female perigonadal fat mass were reduced more by the combination of cancer and prior EtOH than either exposure alone in both males and females. In males, protein synthesis was reduced by 30% following alcohol exposure, while no reductions were observed in female mice. AMPK Thr172 phosphorylation was increased in both male and female EtOH‐Cancer groups, while Akt Thr308 phosphorylation was reduced only among males in EtOH‐Cancer mice. Substrates in the mTORC1 pathway were reduced by cancer in both males and females, but prior alcohol intake only reduced phosphorylation of 4E‐BP1 Ser65 and rpS6 Ser240/244 to a greater extent in male, but not female, mice. Autophagic and proteasomal signaling were largely unaffected by prior alcohol intake in cancer mice, despite a greater increase in Murf1 mRNA in both sexes. Conclusions Prior alcohol consumption accelerates or worsens the onset of certain aspects of cancer cachexia in a sex‐dependent manner, with males being more sensitive to these exposures, even with abstinence from alcohol prior to tumor initiation.

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Acute binge alcohol alters whole body metabolism and the time-dependent expression of skeletal muscle-specific metabolic markers for multiple days in mice

Abstract: Herein, we demonstrate that acute alcohol intoxication immediately alters whole body metabolism coinciding with rapid changes in the skeletal muscle macronutrient gene signature for at least 48 h postbinge and that this response diverges from hepatic effects and those of a fasted animal.

Cited by 12 publications

References 48 publications

Alcohol and Skeletal Muscle in Health and Disease

Alcohol and Skeletal Muscle in Health and Disease

Episodic Binge-like Ethanol Reduces Skeletal Muscle Strength Associated with Atrophy, Fibrosis, and Inflammation in Young Rats

Impact of prior alcohol use on the subsequent development of cancer cachexia in male and female mice

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