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.

CONCLUSION:

Impairments in protein trafficking in AFLD are likely a direct result of alcohol administration, and not a function of fatty liver.

• Authors: Karuna Rasineni, Daniel D Penrice, Sathish Kumar Natarajan, Mark A McNiven, Benita L McVicker, Kusum K Kharbanda, Carol A Casey, Edward N Harris
• Journal: BMC gastroenterology (BMC Gastroenterol) Vol. 16 Pg. 27 (Feb 29 2016) ISSN: 1471-230X [Electronic] England
• PMID: 26924554 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Asialoglycoprotein Receptor
• Bile Acids and Salts
• Membrane Proteins
• Perilipin-2
• RNA, Messenger
• Serum Albumin
• Solvents
• Triglycerides
• rab7 GTP-Binding Proteins
• rab7 GTP-binding proteins, rat
• Ethanol
• Cholesterol
• Alanine Transaminase
• Alkaline Phosphatase
• Rab18 protein, rat
• Rab3d protein, rat
• rab GTP-Binding Proteins
• rab3 GTP-Binding Proteins

Topics

• Alanine Transaminase (metabolism)
• Alkaline Phosphatase (metabolism)
• Animals
• Asialoglycoprotein Receptor (genetics, metabolism)
• Bile Acids and Salts (metabolism)
• Blotting, Western
• Cholesterol (metabolism)
• Diet, High-Fat
• Disease Models, Animal
• Endocytosis (physiology)
• Ethanol (toxicity)
• Fatty Liver, Alcoholic (etiology, metabolism)
• Hepatocytes (metabolism)
• Immunohistochemistry
• Membrane Proteins (metabolism)
• Non-alcoholic Fatty Liver Disease (metabolism)
• Perilipin-2
• RNA, Messenger (metabolism)
• Rats
• Serum Albumin (metabolism)
• Solvents (toxicity)
• Transport Vesicles (metabolism)
• Triglycerides (metabolism)
• rab GTP-Binding Proteins (genetics, metabolism)
• rab3 GTP-Binding Proteins (genetics, metabolism)
• rab7 GTP-Binding Proteins