Evidence map›Paper›PMID 24492484›Full record

ArticleAutophagy2014

Alcohol-induced autophagy contributes to loss in skeletal muscle mass.

Samjhana Thapaliya, Ashok Runkana, Megan R McMullen, Laura E Nagy, Christine McDonald, Sathyamangla V Naga Prasad, Srinivasan Dasarathy

Open access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed, 4 pooled it
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

105 citing papers in PubMed, 4 syntheses or guidelines pooled it, 161 citations in OpenAlex.

  1. Pooled it
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  5. Trial
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  15. Alcohol consumption may not be a risk factor for sarcopenia in the older adults.Experimental biology and medicine (Maywood, N.J.) · 2025
    Article
  16. Article
  17. Review
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  20. Article

45 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Samjhana ThapaliyaDepartment of Pathobiology; Cleveland Clinic; Cleveland, OH USA.
Ashok RunkanaDepartment of Pathobiology; Cleveland Clinic; Cleveland, OH USA; Department of Internal Medicine; Fairview Hospital; Cleveland, OH USA.
Megan R McMullenDepartment of Pathobiology; Cleveland Clinic; Cleveland, OH USA.
Laura E NagyDepartment of Pathobiology; Cleveland Clinic; Cleveland, OH USA; Department of Gastroenterology and Hepatology; Cleveland Clinic; Cleveland, OH USA.
Christine McDonaldDepartment of Pathobiology; Cleveland Clinic; Cleveland, OH USA.
Sathyamangla V Naga PrasadDepartment of Molecular Cardiology; Cleveland Clinic; Cleveland, OH USA.
Srinivasan DasarathyDepartment of Pathobiology; Cleveland Clinic; Cleveland, OH USA; Department of Gastroenterology and Hepatology; Cleveland Clinic; Cleveland, OH USA.
Cleveland Clinic · USFairview Southdale Hospital · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Non Alcoholic Steatohepatitis Clinical Research NetworkU01DK061732 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI Srinivasan Dasarathy · 2002 to 2026
$12.2M
Pilot ProjectP20AA017837 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI NAGY, LAURA E. · 2009 to 2013
$2.2M
Mechanisms of Malnutrition in Cirrhosis with Portosystemic ShuntingR01DK083414 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI DASARATHY, SRINIVASAN · 2011 to 2015
$1.8M
Autophagy and Nod2 Function in Crohn's DiseaseR01DK082437 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI MCDONALD, CHRISTINE L · 2009 to 2013
$1.6M
NCATS NIH HHS UL1 TR000439NIAAA NIH HHS P20 AA017837NIAAA NIH HHS P20- AA 017837NIDDK NIH HHS DK 83414NIDDK NIH HHS R01 DK082437NIDDK NIH HHS R01DK082437NIDDK NIH HHS R01 DK083414NIDDK NIH HHS U01 DK061732
6 · The paper itself

Abstract

Patients with alcoholic cirrhosis and hepatitis have severe muscle loss. Since ethanol impairs skeletal muscle protein synthesis but does not increase ubiquitin proteasome-mediated proteolysis, we investigated whether alcohol-induced autophagy contributes to muscle loss. Autophagy induction was studied in: A) Human skeletal muscle biopsies from alcoholic cirrhotics and controls, B) Gastrocnemius muscle from ethanol and pair-fed mice, and C) Ethanol-exposed murine C2C12 myotubes, by examining the expression of autophagy markers assessed by immunoblotting and real-time PCR. Expression of autophagy genes and markers were increased in skeletal muscle from humans and ethanol-fed mice, and in myotubes following ethanol exposure. Importantly, pulse-chase experiments showed suppression of myotube proteolysis upon ethanol-treatment with the autophagy inhibitor, 3-methyladenine (3MA) and not by MG132, a proteasome inhibitor. Correspondingly, ethanol-treated C2C12 myotubes stably expressing GFP-LC3B showed increased autophagy flux as measured by accumulation of GFP-LC3B vesicles with confocal microscopy. The ethanol-induced increase in LC3B lipidation was reversed upon knockdown of Atg7, a critical autophagy gene and was associated with reversal of the ethanol-induced decrease in myotube diameter. Consistently, CT image analysis of muscle area in alcoholic cirrhotics was significantly reduced compared with control subjects. In order to determine whether ethanol per se or its metabolic product, acetaldehyde, stimulates autophagy, C2C12 myotubes were treated with ethanol in the presence of the alcohol dehydrogenase inhibitor (4-methylpyrazole) or the acetaldehyde dehydrogenase inhibitor (cyanamide). LC3B lipidation increased with acetaldehyde treatment and increased further with the addition of cyanamide. We conclude that muscle autophagy is increased by ethanol exposure and contributes to sarcopenia.

Indexed as

AcetaldehydeAdultAgedAlcoholsAnimalsAutophagyDisease Models, AnimalFemaleHumansMaleMiceMiddle AgedMuscle Fibers, SkeletalMuscle, SkeletalMuscular DiseasesProteolysisAcetaldehydeAlcoholsalcoholautophagyC2C12 myotubesproteasomeproteolysisskeletal muscle

Identifiers

PMID24492484
PMCPMC4091154
OpenAlexW2043837896

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.