Review for 10.1186/s12876-016-0433-4 (2016)

Reviewer ’s report  
 
Title: Alcoholic vs Non -Alcoholic Fatty Liver in Rats: Distinct Differences in Endocytosis and 
Vesicle Trafficking despite Similar Pathology  
 
 
Version: 0 Date: 30 Nov 2015  
 
 
Reviewer: Pamela Tuma  
 
 
Reviewer's report:  
 
 
This manuscript examines whether distinct differences in altered hepatic function are present in 
two models of fatty liver that are histologically similar: non -alcoholic and alcoholic fatty liver 
(NALF and ALF).  They tested several parameters and determined  that the extent of liver injury 
as measured by ALT and ALP, lipid accumulation and oxidative stress was similar in the two 
disease models.  Interestingly, ALF was associated with additional impairments in asialo -
glycoprotein receptor (ASGPR) endocytosis, rab GTPase levels and possible changes in 
cholesterol synthesis.  Although the study is highly descriptive, it is important.  Despite their 
similarity in histology, the mechanisms by which NALF and ALF progress to end -point liver 
injury (fibrosis, hepatiti s, cirrhosis) are likely different and may point to differential therapeutic 
strategies for treating early stages of these diseases.   However, there are a few points that the 
authors might choose to address to enhance the overall impact of these studies.  
 
 
The selection of rab GTPases examined in the manuscript seems a bit arbitrary and incomplete.  
In their earlier studies, rabs 1, 2, 3d, 5, 7 and 18 were examined in post -nuclear supernatants and 
on purified lipid droplets.  In the PNS samples, changes wer e modest in total protein levels, but 
when lipid droplet associations were monitored, changes were much more apparent and 
numerous.  In an effort to be complete, it might be worthwhile to extend these studies to the 
same complement of rabs and their associ ations with lipid droplets from both ALF and NALF 
hepatocytes.   Also, because changes in levels don't necessarily correlate with altered function, it 
might be useful to determine by indirect immunofluorescence the subcellular distributions of the 
rabs (or  selected rabs) in the two disease models.  
 
 
 
Also, since rab7 has been identified as a key regulator of hepatic lipophagy, it would be 
informative to look at different lipophagic/autophagic markers (by immunoblotting and indirect 
immunofluorescence) in the two disease models to see if the decreased rab7 levels correlate with 
changes in lipophagy.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supporte d by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an a dditional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
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