Alcoholic vs non-alcoholic fatty liver in rats: Distinct differences in endocytosis and vesicle trafficking despite similar pathology

Karuna Rasineni, Daniel D. Penrice, Sathish Kumar Natarajan, Mark A. McNiven, Benita L. McVicker, Kusum K. Kharbanda, Carol A. Casey, Edward N. Harris

Research output: Contribution to journalArticle

8 Scopus citations

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 125I- 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 125I- 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.

Original languageEnglish (US)
Article number27
JournalBMC Gastroenterology
Volume16
Issue number1
DOIs
StatePublished - Feb 29 2016

Keywords

  • Alcoholic fatty liver disease (AFLD)
  • Asialoglycoprotein receptor (ASGPR)
  • Non-alcohol fatty liver disease (NAFLD)
  • RabGTPase proteins
  • Receptor-mediated endocytosis

ASJC Scopus subject areas

  • Gastroenterology

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