Dennis R Warner, Jeffrey B Warner, Yasmeen Abdelfadil, Josiah E Hardesty, Rui Treves, Chao Lei, Hannah E Hanford, Craig J McClain, Irina A Kirpich
{"title":"Effects of soluble epoxide hydrolase inhibition on liver injury and gut microbiota in mice chronically fed ethanol.","authors":"Dennis R Warner, Jeffrey B Warner, Yasmeen Abdelfadil, Josiah E Hardesty, Rui Treves, Chao Lei, Hannah E Hanford, Craig J McClain, Irina A Kirpich","doi":"10.1111/acer.70109","DOIUrl":"10.1111/acer.70109","url":null,"abstract":"<p><strong>Background: </strong>Alcohol-associated liver disease (ALD) is a significant global health concern, with limited effective treatments currently available. Targeting a specific pathway of polyunsaturated fatty acid (PUFA) metabolism, in which beneficial FA-derived compounds, known as epoxy fatty acids (EpFAs), are rapidly converted into less active or inactive metabolites by the enzyme, soluble epoxide hydrolase (s-EH), has shown promise in treating various pathological conditions. In this study, the s-EH inhibitor, t-TUCB, was tested for its efficacy in attenuating liver damage induced by chronic ethanol (EtOH) consumption in an animal model that mimics early-stage ALD in humans.</p><p><strong>Methods: </strong>C57BL6/J male mice were fed an EtOH-containing diet with or without t-TUCB for 8 weeks. Liver steatosis, inflammation, and injury were evaluated. Fecal 16S rRNA sequencing was performed to examine the impact of s-EH inhibition on the gut microbiota composition.</p><p><strong>Results: </strong>EtOH-induced liver injury was attenuated in t-TUCB-treated mice, with a notable decrease in endoplasmic reticulum stress, hepatocyte cell death, and proinflammatory cytokine expression. There was no effect of t-TUCB on EtOH-induced hepatic steatosis. t-TUCB treatment shifted the liver lipid profile, increasing several EpFAs, such as 17,18-EpETE and 19,20-EpDPA. These EpFAs decreased apoptosis and LPS-induced expression of proinflammatory cytokines in vitro. t-TUCB treatment significantly increased Akkermansia muciniphila, a species known for its beneficial properties, in control but not in EtOH-fed mice. The EtOH-induced increase in bacteria taxa previously associated with liver injury, including the Peptostreptococcaceae family and the species, Alistipes massieliensis, was reduced in t-TUCB-treated mice.</p><p><strong>Conclusions: </strong>Our data demonstrate the beneficial effects of t-TUCB treatment on chronic EtOH-induced liver injury and gut microbiota imbalances, in turn, promoting liver health. These findings suggest that pharmacologic s-EH inhibition may serve as a promising strategy for reducing liver injury in ALD.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mollie A Monnig, Philip S Lamb, Samantha E Clark, Peter M Monti
{"title":"Acute changes in immune biomarkers under low- and moderate-dose alcohol in light and heavy drinkers: A randomized, placebo-controlled trial.","authors":"Mollie A Monnig, Philip S Lamb, Samantha E Clark, Peter M Monti","doi":"10.1111/acer.70106","DOIUrl":"10.1111/acer.70106","url":null,"abstract":"<p><strong>Background: </strong>Alcohol consumption modulates immune function, in part by promoting microbial translocation. This process is thought to trigger an acute-phase immune response, contributing to alcohol-related immune modulation. However, most evidence on these effects arises from preclinical models. Additionally, existing human studies lack a placebo control, rely on a single alcohol dose, or fail to account for individual drinking history.</p><p><strong>Methods: </strong>This study examined in vivo concentrations of lipopolysaccharide (LPS, a marker of microbial translocation), acute-phase proteins, cytokines, and chemokines under low-dose alcohol, moderate-dose alcohol, and placebo using a within-subjects design in light and heavy drinkers. Participants (N = 32) were light drinkers (n = 15) and nontreatment-seeking heavy drinkers (n = 17). Groups did not differ on demographics. Participants received each dose condition in randomized order. Blood samples were collected at baseline and at hourly intervals for 4 h. Plasma concentrations of LPS, acute-phase proteins (LPS binding protein [LBP], soluble cluster of differentiation 14 [sCD14], and soluble cluster of differentiation 163 [sCD163]), and cytokines/chemokines (interleukin 6 [IL-6], interleukin 8 [IL-8], interleukin 10 [IL-10], monocyte chemoattractant protein [MCP-1], and tumor necrosis factor alpha [TNF-α]) were quantified using immunoassays. Linear mixed models tested effects of dose condition, drinker group, time, and the three-way interaction. Further analyses tested associations of LPS, LBP, sCD14, and sCD163 with cytokines/chemokines.</p><p><strong>Results: </strong>The three-way interaction of dose by group by time was significant for IL-6 (p = 0.042), IL-8 (p = 0.039), MCP-1 (p = 0.001), and TNF-α (p = 0.001). LPS was associated with concentrations of interleukins. Levels of sCD163 were 43% higher in heavy drinkers overall. Heavy drinkers exhibited apparent conditioned peripheral immune suppression, wherein the expectation of alcohol elicited selective immunosuppressive responses.</p><p><strong>Conclusions: </strong>This study offers novel in vivo evidence that alcohol-induced changes in immune function are dependent on both acute dose and chronic drinking behavior.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kelly A Hewitt, Skylar E Nicholson, Madilyn J Peterson, Lucas L Dwiel, Angela M Henricks
{"title":"Chronic intermittent alcohol yields sex-specific disruptions in cortical-striatal-limbic oscillations in rats.","authors":"Kelly A Hewitt, Skylar E Nicholson, Madilyn J Peterson, Lucas L Dwiel, Angela M Henricks","doi":"10.1111/acer.70111","DOIUrl":"https://doi.org/10.1111/acer.70111","url":null,"abstract":"<p><strong>Background: </strong>There are significant sex differences in the causes and consequences of alcohol misuse, suggesting that sex-specific neurobiological mechanisms might drive drinking. The current study used a rodent model to determine whether chronic intermittent alcohol exposure impacts cortical, striatal, and limbic neural circuits in a sex-specific manner.</p><p><strong>Methods: </strong>Female and male Sprague-Dawley rats were trained to self-administer 10% alcohol before implanting bilateral electrodes into the infralimbic cortex (IL), nucleus accumbens shell (NAcSh), and central nucleus of the amygdala (CeA). Half of the rats were then exposed to 4 weeks of chronic intermittent alcohol (CIA) vapor. During acute withdrawal, local field potentials (LFPs) were recorded in the IL, NAcSh, and CeA. Using an unbiased machine learning approach, we built predictive models to determine whether/which LFP features could distinguish CIA-exposed from control rats in each sex. Real and permuted model performance is reported as average area under the receiver operating curve (AUC).</p><p><strong>Results: </strong>Acute withdrawal was associated with increased alcohol self-administration in males (p < 0.05), but not in females (p > 0.05). Models built from all LFP data performed significantly better than chance in each sex (females AUC: 0.88; males AUC: 0.63). However, when models were restricted, those built on IL and CeA LFPs performed best in females (females AUC: 0.83; males AUC: 0.65), while those built on IL and NAcSh LFPs performed the best in males (males AUC: 0.78; females AUC: 0.57). Individual LFP features that best predicted CIA exposure were also sex-specific, with CeA features predicting CIA exposure in females and corticostriatal features predicting CIA exposure in males.</p><p><strong>Conclusions: </strong>These data support the hypothesis that the neural circuits impacted by chronic alcohol exposure are sex-specific, and significantly add to our understanding of the neurobiological underpinnings behind the sex differences observed in alcohol misuse, offering promising biomarkers for future therapeutic research.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kasey G Creswell, Brooke J Arterberry, Megan E Patrick
{"title":"Historical trends in young adult solitary alcohol use by age and sex from 1977 to 2022.","authors":"Kasey G Creswell, Brooke J Arterberry, Megan E Patrick","doi":"10.1111/acer.70103","DOIUrl":"https://doi.org/10.1111/acer.70103","url":null,"abstract":"<p><strong>Background: </strong>Solitary alcohol use among young adults is a risky drinking behavior associated with concurrent and future alcohol use disorder (AUD) and negative psychosocial outcomes. However, data on its prevalence and historical trends in the general population are limited. We examined historical trends in solitary alcohol use among US young adults (aged 19-30) by age and sex over a 46-year period.</p><p><strong>Methods: </strong>Data were from the Monitoring the Future (MTF) Panel study collected between 1977 and 2022. The sample included 12,851 participants (51.6% female) who reported past-year alcohol use and completed surveys at ages 19/20, 21/22, 23/24, 25/26, 27/28, and 29/30. Solitary alcohol use was assessed by self-report of drinking alone in the past year. Joinpoint regression analyses examined historical trends in the prevalence of solitary alcohol use by age and sex.</p><p><strong>Results: </strong>Approximately 40% of those who used alcohol in the past year reported engaging in solitary alcohol use at least once in the past year. Across all age groups, the prevalence of past-year solitary alcohol use initially decreased and then increased over time. Significant joinpoints indicated shifts in trends beginning in the mid-1990s to early 2000s, with increases more pronounced among females.</p><p><strong>Conclusions: </strong>The prevalence of solitary alcohol use among US young adults has increased in recent decades, to levels on par with what was observed in the late 1970s. Particular increases among females since late 1990s/early 2000s have narrowed the traditional sex gap in this risky drinking behavior. Given the association of solitary drinking with concurrent and future alcohol problems, these findings highlight the need for continued monitoring of solitary alcohol use among young adults, especially females.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriel P A Costa, Rebecca Suh, Julio C Nunes, Brian Pittman, Mehmet Sofuoglu, Ismene Petrakis, Joao P De Aquino
{"title":"Pain interference, alcohol use, and metabolic health: Insights from a nationally representative study.","authors":"Gabriel P A Costa, Rebecca Suh, Julio C Nunes, Brian Pittman, Mehmet Sofuoglu, Ismene Petrakis, Joao P De Aquino","doi":"10.1111/acer.70108","DOIUrl":"https://doi.org/10.1111/acer.70108","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain, heavy alcohol use, and metabolic dysfunction frequently cooccur, yet their interrelationships remain inadequately characterized, contributing to fragmented therapeutic approaches. This study quantifies independent and interactive associations between these conditions and pain interference in a nationally representative sample.</p><p><strong>Methods: </strong>We conducted a cross-sectional analysis of 30,442 adults (51.1% women) participating in the 2007-2012 National Health and Nutrition Examination Survey (NHANES), representing an estimated 301,890,165 US adults. Primary exposures included heavy alcohol use (defined by National Institute on Alcohol Abuse and Alcoholism criteria), metabolic dysfunction (indexed by obesity status, Triglyceride-Glucose Index [TyG], and Systemic Inflammation Index [SII]), and sleep duration. Our main outcome was pain interference, measured as days in the past 30 days during which pain disrupted usual activities. We utilized survey-weighted quasi-Poisson regression models, adjusting for age, gender, and race/ethnicity.</p><p><strong>Results: </strong>Heavy alcohol use was independently associated with 34% more days of pain interference (IRR = 1.34, 95% CI = 1.16-1.55), while obesity was associated with a 50% increase (IRR = 1.50, 95% CI = 1.35-1.67). Higher TyG (IRR = 1.19, 95% CI = 1.10-1.30) and SII (IRR = 1.01, 95% CI = 1.01-1.02) were also consistently associated with increased pain interference. The interaction between heavy alcohol use and obesity suggested additive rather than synergistic effects (IRR = 0.82, 95% CI = 0.65-1.05). Each additional hour of sleep was associated with a 14% reduction in pain interference (IRR = 0.86, 95% CI = 0.83-0.88). In a secondary analysis (n = 9756), higher physical activity was associated with 10% fewer days of pain interference (IRR = 0.90, 95% CI = 0.87-0.93).</p><p><strong>Conclusions: </strong>Heavy alcohol use and metabolic dysfunction demonstrate independent, additive effects on pain interference, with concurrent conditions corresponding to maximal days of pain interference. Sleep duration and physical activity emerge as potentially modifiable protective factors. These findings support the implementation of integrated therapeutic approaches targeting multiple pathophysiological domains to optimize clinical outcomes in this complex patient population.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144499591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biomedical and behavioral research on alcohol and youth: Celebrating the alcohol research career achievements of Dr. Linda Patia Spear.","authors":"Marisa M Silveri","doi":"10.1111/acer.70104","DOIUrl":"10.1111/acer.70104","url":null,"abstract":"","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter Næsborg Schøler, Anette Søgaard Nielsen, Katie Witkiewitz, Michael Bogenschutz, Randi Bilberg, Angelina Isabella Mellentin, Kjeld Andersen
{"title":"Relief craving severity moderates nonpharmacological treatment outcomes in treatment-seeking older adults with alcohol use disorder.","authors":"Peter Næsborg Schøler, Anette Søgaard Nielsen, Katie Witkiewitz, Michael Bogenschutz, Randi Bilberg, Angelina Isabella Mellentin, Kjeld Andersen","doi":"10.1111/acer.70097","DOIUrl":"https://doi.org/10.1111/acer.70097","url":null,"abstract":"<p><strong>Background: </strong>Craving alcohol for reward (positive reinforcement) and relief (negative reinforcement) has been proposed as useful phenotypes for precision medicine approaches to alcohol use disorder (AUD) treatment. This study examined reward and relief craving in nonpharmacological treatments, Motivational Enhancement Therapy (MET) versus MET + Community Reinforcement Approach (CRA), among older adults.</p><p><strong>Methods: </strong>Secondary analyses of data from The Elderly Study (N = 693; mean age 64.0 years; male 59.7%), a single-blinded, multisite, randomized controlled trial of two nonpharmacological treatments in an elderly population (60+ years) diagnosed with DSM-5 AUD. Latent profile analysis (LPA) was used to identify craving profiles based on The Alcohol Abstinence Self-Efficacy Scale (AASE) temptation subscale scores. The classification performance of clinical cutoff scores on the AASE scale was tested against the LPA solution. Associations between cutoff-based craving groups and treatment success (binary variable representing change in alcohol consumption and quality of life across profiles pre-/posttreatment) were analyzed using logistic regression, stratified on MET versus MET + CRA. Differences in alcohol consumption and quality of life scores pre-/posttreatment were analyzed using the Wilcoxon signed-rank test.</p><p><strong>Results: </strong>Four reward-relief craving profiles were identified but were more distinguished by variation in relief craving (low relief, medium-low relief, medium-high relief, and high relief). Compared to the low relief craving group, the medium-high relief craving group had lower odds for treatment success when receiving MET: adjusted Odds Ratio (aOR) 0.42 (95% CI 0.21-0.84), and the high relief craving group had lower odds for treatment success when receiving MET + CRA: aOR 0.38 (95% CI 0.15-0.94). Alcohol consumption was reduced, and psychological quality of life was improved at follow-up across all relief craving groups.</p><p><strong>Conclusion: </strong>This study identified reward and relief drinking craving among older adults with AUD. Results indicate that considering relief craving when offering nonpharmacological treatment to older adults suffering from AUD may be clinically relevant.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Articles of Public Interest","authors":"","doi":"10.1111/acer.70096","DOIUrl":"https://doi.org/10.1111/acer.70096","url":null,"abstract":"","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C Kautz-Turnbull, M Rockhold, E Speybroeck, J Myers, C L M Petrenko
{"title":"Preventing exclusionary discipline and adverse life experiences in FASD: Teachers' ability to recognize students with FASD in the classroom and develop and implement preventative strategies to support learning and behavior.","authors":"C Kautz-Turnbull, M Rockhold, E Speybroeck, J Myers, C L M Petrenko","doi":"10.1111/acer.70100","DOIUrl":"https://doi.org/10.1111/acer.70100","url":null,"abstract":"<p><strong>Background: </strong>People with fetal alcohol spectrum disorders (FASD) experience significant behavioral and academic challenges and high rates of exclusionary discipline practices (EDP). This study investigated teachers' perspectives on barriers and facilitators to recognizing students with FASD in the classroom, and how teachers develop and use preventative strategies to support students with FASD.</p><p><strong>Methods: </strong>Qualitative interviews were conducted with 23 teachers with experience educating students with FASD. Data analysis used a phenomenological approach and content analysis.</p><p><strong>Results: </strong>Teachers identified barriers to recognition of students with FASD, including lack of diagnosis, stigma and discrimination, variability and inconsistency in skills, and compensatory strategies. Experienced teachers could recognize students with FASD and effectively supported students by tailoring existing strategies to the student's profile, building a positive relationship with the student, reframing their understanding of the student's behavior, and collaborating with others.</p><p><strong>Conclusions: </strong>Results indicate experienced teachers' potential to reduce adverse outcomes and EDP for students with FASD.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Upregulation of E3 ligase UBR2 in acetaldehyde-treated C2C12 myotubes and its potential involvement in fast-twitch muscle atrophy in alcohol-fed rats.","authors":"Kaori Shintani-Ishida, Hiroshi Ikegaya","doi":"10.1111/acer.70102","DOIUrl":"https://doi.org/10.1111/acer.70102","url":null,"abstract":"<p><strong>Background: </strong>Chronic alcohol intake induces atrophy of type II (anaerobic, fast-twitch) muscle fibers in preference to type I (aerobic, slow-twitch) muscle fibers. However, the molecular mechanism underlying the preferential atrophy of type II muscle fibers remains unclear. The ubiquitin-proteasome system (UPS) mediates the degradation of myofibrillar proteins in skeletal muscle loss. This study investigated whether E3 ubiquitin ligases, including UBR2 and MuRF1, are involved in ethanol-induced type II muscle fiber-specific atrophy.</p><p><strong>Methods: </strong>In a chronic alcohol intake rat model, 4- to 5-week-old male Wistar rats were fed the Lieber-DeCarli liquid diet for 8 weeks. Muscle specimens were collected from the extensor digitorum longus (EDL) and soleus muscles of both legs. In an in vitro model, myotubes differentiated from murine C2C12 myoblasts were treated with culture medium containing 100 mM ethanol or 1 mM acetaldehyde for 6 h.</p><p><strong>Results: </strong>The muscle weight of the EDL seemed to be lesser in the ethanol group compared to the control group, and there was no difference in the muscle weight of the soleus between these groups. Cross-sectional area (CSA) of type IIA, IIB, and IIX muscle fibers in the EDL of ethanol-fed rats was smaller compared to the control rats, and CSA of type I muscle fibers in the soleus was larger in ethanol-fed rats. UBR2 protein levels seem to increase in the EDL but not in the soleus, whereas MuRF1 protein level remained unchanged in both muscles. C2C12 myotubes expressing MHC IIb, characteristics of type IIB muscle fibers, showed reduced myotube diameter after ethanol or acetaldehyde treatment. Acetaldehyde treatment increased UBR2 expression, but not MuRF1 expression, and enhanced ubiquitination. Knockdown of UBR2 using siRNA prevented acetaldehyde-induced myotube atrophy.</p><p><strong>Conclusion: </strong>This study demonstrated that the E3 ligase UBR2 may play a role in alcohol-induced type II muscle-preferential atrophy.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}