Ethanol Induces Skeletal Muscle Autophagy

Study Overview
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Brief Summary
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In this study we plan to demonstrate that ethanol induces skeletal muscle autophagy to degrade MAA adducts.

Detailed Description
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Hypothesis: Ethanol mediated modification of skeletal muscle proteins to form MAA adducts that in turn induce skeletal muscle autophagy. Patients with alcoholic steatosis, hepatitis and cirrhosis (n=10 each) will be recruited from the liver transplant nutrition clinic or the hepatology inpatient service and their body composition quantified using anthropometry, bioelectrical impedance analysis, CT image analysis and DEXA if available. Control Subjects. Controls will be recruited by advertisement. All control subjects will have a normal clinical history, physical examination, and screening chemistries. They will not have any significant medical conditions requiring the use of medications. Their nutritional status within 20% of normal as defined by ideal body weight.

Official Title
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Mechanisms of Skeletal Muscle Proteolysis With Ethanol Consumption: an Integrated Molecular Metabolic Approach

Conditions
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Alcoholic Liver Disease

Intervention / Treatment
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* Other: Biopsies


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Alcoholic liver disease: clinical, biochemical, imaging criteria and liver biopsy where available Age 18 - 65 years old Controls: Serum liver transaminases (i.e. ALT and AST) 40 IU/L Normal liver ultrasound Age 18 - 65 years old Exclusion Criteria: For both groups - alcoholic liver disease and controls: Poorly controlled diabetes mellitus (HbA1C>9.5 g/dl) Untreated Hyper- / hypo- thyroidism Patients on dialysis, renal disease with serum creatinine 1.5 mg/dL Active intravenous drug use History of bowel surgery or gastric bypass surgery Medications known to alter muscle protein metabolism (i.e. corticosteroids, tamoxifen, high-dose estrogen, testosterone or anabolic steroids) Metastatic disease, Advanced cardiac or pulmonary disease Pregnancy Coagulopathy- INR >1.4 and platelet count <80,000/ml.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Alcoholic Steatosis<br>This group will have 10 patients with alcoholic steatosis which is milder disease and muscle biopsies will be performed | Other: Biopsies<br>* Biopsy will be done on the Vastus Lateralis muscle in all groups<br>|
| Cirrhosis<br>This group will consist of 10 patients with cirrhosis. We anticipate a 50% difference in these patients and the controls in the autophagy readouts and muscle biopsies will be performed | Other: Biopsies<br>* Biopsy will be done on the Vastus Lateralis muscle in all groups<br>|
| Steatohepatitis<br>This group will have 10 patients with alcoholic steatohepatitis that have more severe necroinflammation in the liver but for a shorter duration of illness and muscle biopsies will be performed | Other: Biopsies<br>* Biopsy will be done on the Vastus Lateralis muscle in all groups<br>|
| controls<br>This group will consist of 10 patients who are healthy and have no liver disease diagnosis and muscle biopsies will be performed | Other: Biopsies<br>* Biopsy will be done on the Vastus Lateralis muscle in all groups<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal Muscle Autophagy | We will measure Malonyldialdehyde Acetaldehyde protein adducts to see skeletal muscle proteolysis during a one time muscle biopsy | 4 hours |