Reviewer ’s report  
 
Title: Western diet -induced hepatic steatosis and alterations in the liver transcriptome in adult  
Brown -Norway rats  
 
Version: 0 Date: 22 Aug 2015  
 
Reviewer: Chris Corton  
 
Reviewer's report:  
 
Roberts et al.  
 
This manuscript describes the phenotypic and gene expression effects of a relatively short t erm 
feeding of a western diet in rats.  The authors performed RNA -Seq analysis of the livers and 
found some expected changes in the genes involved in lipid homeostasis especially decreases in 
cholesterol synthesis genes.  In contrast to other studies that assessed changes after the 6 week 
time point, the authors found little evidence of steatohepatitus but did find some changes in 
markers of inflammation and the acute phase response.  Overall the results were clear and well 
presented and the conclusions wer e supported by the results.  
 
The main concern this reviewer has is the significance of the work as many studies have been 
published over the years on determination of the effects of a western diet in the livers of rodents.  
It would be useful to the reader  to clearly articulate the unique aspects of the study and maybe 
this could be put into the introduction as to how the present study is unique.  In the discussion, 
there could be an expansion of the discussion of the timing of effects including the differe nt 
stages of fatty liver disease and progression putting into context the present study.  
 
Given the relatively low number of gene expression changes, the authors should consider using 
the RNA -Seq data to examine if the western diet led to differential spli cing events that would be 
potentially overlooked in an analysis of transcript abundance.  This seems to be a relatively 
untouched area in the field and could bring in the potential for linking the steatosis to altered 
function of critical lipid homeostasis  genes.  
 
The authors did not include in the analysis of the liver weights.  Is this not an expected endpoint 
to include in these types of studies?  
 
Minor point  
The authors should stick to standard nomenclature for the genes in rats and mice.  For example, 
genes should be italicized.  
 
 
 
 
 
 
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 supported 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 additional 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  
Please complete a declaration of competing interests, considering the following question s: 
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or sha res in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you re ceived reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interes ts in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the websi te along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my name d report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Western diet -induced hepatic steatosis and alterations in the liver transcriptome in adult  
Brown -Norway rats  
 
Version: 0 Date: 22 Aug 2015  
 
Reviewer: Chris Corton  
 
Reviewer's report:  
 
Roberts et al.  
 
This manuscript describes the phenotypic and gene expression effects of a relatively short t erm 
feeding of a western diet in rats.  The authors performed RNA -Seq analysis of the livers and 
found some expected changes in the genes involved in lipid homeostasis especially decreases in 
cholesterol synthesis genes.  In contrast to other studies that assessed changes after the 6 week 
time point, the authors found little evidence of steatohepatitus but did find some changes in 
markers of inflammation and the acute phase response.  Overall the results were clear and well 
presented and the conclusions wer e supported by the results.  
 
The main concern this reviewer has is the significance of the work as many studies have been 
published over the years on determination of the effects of a western diet in the livers of rodents.  
It would be useful to the reader  to clearly articulate the unique aspects of the study and maybe 
this could be put into the introduction as to how the present study is unique.  In the discussion, 
there could be an expansion of the discussion of the timing of effects including the differe nt 
stages of fatty liver disease and progression putting into context the present study.  
 
Given the relatively low number of gene expression changes, the authors should consider using 
the RNA -Seq data to examine if the western diet led to differential spli cing events that would be 
potentially overlooked in an analysis of transcript abundance.  This seems to be a relatively 
untouched area in the field and could bring in the potential for linking the steatosis to altered 
function of critical lipid homeostasis  genes.  
 
The authors did not include in the analysis of the liver weights.  Is this not an expected endpoint 
to include in these types of studies?  
 
Minor point  
The authors should stick to standard nomenclature for the genes in rats and mice.  For example, 
genes should be italicized.  
 
 
 
 
 
 
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 supported 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 additional 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  
Please complete a declaration of competing interests, considering the following question s: 
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or sha res in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you re ceived reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interes ts in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the websi te along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my name d report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Western diet -induced hepatic steatosis and alterations in the liver transcriptome in adult  
Brown -Norway rats  
 
Version: 0 Date: 22 Aug 2015  
 
Reviewer: Chris Corton  
 
Reviewer's report:  
 
Roberts et al.  
 
This manuscript describes the phenotypic and gene expression effects of a relatively short t erm 
feeding of a western diet in rats.  The authors performed RNA -Seq analysis of the livers and 
found some expected changes in the genes involved in lipid homeostasis especially decreases in 
cholesterol synthesis genes.  In contrast to other studies that assessed changes after the 6 week 
time point, the authors found little evidence of steatohepatitus but did find some changes in 
markers of inflammation and the acute phase response.  Overall the results were clear and well 
presented and the conclusions wer e supported by the results.  
 
The main concern this reviewer has is the significance of the work as many studies have been 
published over the years on determination of the effects of a western diet in the livers of rodents.  
It would be useful to the reader  to clearly articulate the unique aspects of the study and maybe 
this could be put into the introduction as to how the present study is unique.  In the discussion, 
there could be an expansion of the discussion of the timing of effects including the differe nt 
stages of fatty liver disease and progression putting into context the present study.  
 
Given the relatively low number of gene expression changes, the authors should consider using 
the RNA -Seq data to examine if the western diet led to differential spli cing events that would be 
potentially overlooked in an analysis of transcript abundance.  This seems to be a relatively 
untouched area in the field and could bring in the potential for linking the steatosis to altered 
function of critical lipid homeostasis  genes.  
 
The authors did not include in the analysis of the liver weights.  Is this not an expected endpoint 
to include in these types of studies?  
 
Minor point  
The authors should stick to standard nomenclature for the genes in rats and mice.  For example, 
genes should be italicized.  
 
 
 
 
 
 
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 supported 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 additional 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  
Please complete a declaration of competing interests, considering the following question s: 
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or sha res in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you re ceived reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interes ts in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the websi te along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my name d report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant