Alcoholic vs non-alcoholic fatty liver in rats

Distinct differences in endocytosis and vesicle trafficking despite similar pathology

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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

Fingerprint

Fatty Liver
Endocytosis
Protein Transport
Pathology
Liver
Hepatocytes
Fats
Alcohols
Triglycerides
Fibrosis
Alcoholic Fatty Liver
Protein Carbonylation
Asialoglycoprotein Receptor
Alcoholic Liver Diseases
Wounds and Injuries
Serum
Lipid Peroxidation
Hepatitis
Glutathione
Non-alcoholic Fatty Liver Disease

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

Cite this

@article{e2d524af20bb48c69d49487e77009e81,
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 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.",
keywords = "Alcoholic fatty liver disease (AFLD), Asialoglycoprotein receptor (ASGPR), Non-alcohol fatty liver disease (NAFLD), RabGTPase proteins, Receptor-mediated endocytosis",
author = "Karuna Rasineni and Penrice, {Daniel D.} and Natarajan, {Sathish K} and McNiven, {Mark A.} and McVicker, {Benita L} and Kusum Kharbanda and Casey, {Carol A} and Harris, {Edward N}",
year = "2016",
month = "2",
day = "29",
doi = "10.1186/s12876-016-0433-4",
language = "English (US)",
volume = "16",
journal = "BMC Gastroenterology",
issn = "1471-230X",
publisher = "BioMed Central",
number = "1",

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TY - JOUR

T1 - Alcoholic vs non-alcoholic fatty liver in rats

T2 - Distinct differences in endocytosis and vesicle trafficking despite similar pathology

AU - Rasineni, Karuna

AU - Penrice, Daniel D.

AU - Natarajan, Sathish K

AU - McNiven, Mark A.

AU - McVicker, Benita L

AU - Kharbanda, Kusum

AU - Casey, Carol A

AU - Harris, Edward N

PY - 2016/2/29

Y1 - 2016/2/29

N2 - 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.

AB - 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.

KW - Alcoholic fatty liver disease (AFLD)

KW - Asialoglycoprotein receptor (ASGPR)

KW - Non-alcohol fatty liver disease (NAFLD)

KW - RabGTPase proteins

KW - Receptor-mediated endocytosis

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U2 - 10.1186/s12876-016-0433-4

DO - 10.1186/s12876-016-0433-4

M3 - Article

VL - 16

JO - BMC Gastroenterology

JF - BMC Gastroenterology

SN - 1471-230X

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