title: Alcoholic vs non-alcoholic fatty liver in rats: distinct differences in endocytosis and vesicle trafficking despite similar pathology.
abstract: BACKGROUND
  Non-alcoholic and alcoholic fatty liver disease (NAFLD and AFLD, respectively) are major health problems, as patients with either condition can progress to hepatitis, fibrosis, and cirrhosis. Although histologically similar, key differences likely exist in these two models. For example, altered content of several vesicle trafficking proteins have been identified in AFLD, but their content in NAFLD is unknown. In this study, we compared select parameters in NAFLD and AFLD in a rat model.
  
  
  METHODS
  We fed either Lieber- DeCarli liquid control or alcohol-containing (35 % as calories) diet (AFLD model) or lean or high-fat (12 or 60 % derived from fat, respectively) pellets (NAFLD model) for 8-10 weeks, n = 8 in each model. Serum, hepatocytes and liver tissue were analyzed. Liver injury markers were measured in serum, triglyceride content and endocytosis (binding and internalization of (125)I- asialoorosomucoid) was measured in isolated hepatocytes, and content of selected trafficking proteins (Rab3D, Rab7 and Rab18) were determined in whole liver tissue.
  
  
  RESULTS
  Although liver injury markers and triglyceride content were similar in both models, binding and internalization of (125)I- asialoorosomucoid was significantly impaired in the hepatocytes from AFLD, but not NAFLD, animals. In addition, protein content of the asialoglycoprotein receptor (ASGPR) and three trafficking proteins, Rab3D, Rab7and Rab18, were significantly decreased after alcohol, but not high-fat feeding. Levels of protein carbonylation, amount of glutathione stores, and lipid peroxidation were similar irrespective of the insult to the livers that resulted in fatty liver.
  
  
  CONCLUSIONS
  Impairments in protein trafficking in AFLD are likely a direct result of alcohol administration, and not a function of fatty liver.
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. rasinenik@gmail.com.|The Liver Study Unit, VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA. rasinenik@gmail.com.
authors.forename: Karuna
authors.initials: K
authors.lastname: Rasineni
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. Daniel.penrice@unmc.edu.|The Liver Study Unit, VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA. Daniel.penrice@unmc.edu.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Penrice
authors.affiliation: Dept. of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA. snatarajan2@unl.edu.
authors.forename: Sathish Kumar
authors.initials: SK
authors.lastname: Natarajan
authors.affiliation: Department of Biochemistry and Molecular Biology and the Center for Digestive Diseases, Mayo Clinic, Rochester, MN, USA. mmcniven@mayo.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: McNiven
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. bmcvicker@unmc.edu.|The Liver Study Unit, VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA. bmcvicker@unmc.edu.
authors.forename: Benita L
authors.initials: BL
authors.lastname: McVicker
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. kkharbanda@unmc.edu.|The Liver Study Unit, VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA. kkharbanda@unmc.edu.|Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. kkharbanda@unmc.edu.
authors.forename: Kusum K
authors.initials: KK
authors.lastname: Kharbanda
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. ccasey@unmc.edu.|The Liver Study Unit, VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA. ccasey@unmc.edu.|Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. ccasey@unmc.edu.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Casey
authors.affiliation: Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, USA. eharris5@unl.edu.
authors.forename: Edward N
authors.initials: EN
authors.lastname: Harris
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000235:genetics / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D015153:Blotting, Western; D002784:Cholesterol / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004705:Endocytosis / Q000502:physiology*; D000431:Ethanol / Q000633:toxicity; D005235:Fatty Liver, Alcoholic / Q000209:etiology / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D000070780:Perilipin-2; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism; D012997:Solvents / Q000633:toxicity; D022161:Transport Vesicles / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D037263:Asialoglycoprotein Receptor; D001647:Bile Acids and Salts; D008565:Membrane Proteins; D000070780:Perilipin-2; D012333:RNA, Messenger; D012709:Serum Albumin; D012997:Solvents; D014280:Triglycerides; D000090802:rab7 GTP-Binding Proteins; C000716466:rab7 GTP-binding proteins, rat; D000431:Ethanol; D002784:Cholesterol; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; C522121:Rab18 protein, rat; C492133:Rab3d protein, rat; D020691:rab GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins