Reviewer ’s report  
 
Title:  The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and 
NASH when fed a western diet supplemented with fructose  
 
Version: 1 Date: 16 Jan 2019 
 
Reviewer:  Reviewer  2 
 
Reviewer’s report:  
 
PEER REVIEWER ASSESSMENTS:  
 
 
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research 
question(s) (brief or other article types: is there a clear objective)?  
 
Yes - there is a clear objective  
 
 
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the 
objectiv e? 
 
Yes - the approach is appropriate  
 
 
EXECUTION - Are the experiments and analyses performed with technical rigor to allow 
confidence in the results?  
 
Yes - experiments and analyses were performed appropriately  
 
 
Statistics - Is the use of statistics in the manuscript appropriate?  
 
Not sure - I am not able to assess the statistics in this study  
 
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
 
Yes - the author's  interpretation is reasonable  
 
 
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically 
sound? If not, can revisions be made to make the work technically sound?  
 
Yes - current version is technically sound  
 
 
PEER REVIEWER COMMENTS:  
 
GEN ERAL COMMENTS: This study is conducted appropriately to determine if the FATZO 
mice fed a western type diet supplemented with fructose is a suitable 0re clinical NASH model. 
The authors have used suitable animal numbers, allocated them randomly to the diff erent 
treatment groups and had someone blinded to the study design perform the histology analysis.  
 
 
REQUESTED REVISIONS:  
 
Authors need to clarify the statistical analysis used here as it is unclear if they used a one way 
ANOVA or a t test. If they used bo th they need to precise in the figure legends which analysis is 
used for which figure.  
 
In addition it is surprising not to see histology data for the liver of the mice on diet for 8and 12 
weeks as they were planned in the study design and blood was used fo r blood chemistry. It 
would be interesting to see the progression of the liver pathology along the full time of the study 
rather than just seeing endpoint.  
 
Finally how can the authors explain that the mice lose fat mass after 4 weeks of diet while their 
body weight steadily increases?  
 
 
ADDITIONAL REQUESTS/SUGGESTIONS:  
 
Get grammatical check as they are some typos in the manuscript  
 
Note: This reviewer report can be downloaded - see attached pdf file.  
 
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 recommend additional statistical review  
 
Quality of written English  
Please indicate th e quality of language in the manuscript:  
 
Needs some language corrections before being publi shed 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
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 shares 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 received reimbursements, fees, funding, or sa lary 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 interests in relation to this paper?  
 
If you can answe r 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.  
 
This reviewer has been re cruited by a partner organization, Research Square. Reviewers with 
declared or apparent competing interests are not utilized for these reviews. This reviewer has 
agreed to publication of their comments online under a Creative Commons Attribution License 
attributed to Research Square and was paid a small honorarium for completing the review within 
a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer 
recommendation.  
 
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 website along with the authors' 
responses. I agree for my report to be m ade 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 named 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:  The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and 
NASH when fed a western diet supplemented with fructose  
 
Version: 1 Date: 16 Jan 2019 
 
Reviewer:  Reviewer  2 
 
Reviewer’s report:  
 
PEER REVIEWER ASSESSMENTS:  
 
 
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research 
question(s) (brief or other article types: is there a clear objective)?  
 
Yes - there is a clear objective  
 
 
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the 
objectiv e? 
 
Yes - the approach is appropriate  
 
 
EXECUTION - Are the experiments and analyses performed with technical rigor to allow 
confidence in the results?  
 
Yes - experiments and analyses were performed appropriately  
 
 
Statistics - Is the use of statistics in the manuscript appropriate?  
 
Not sure - I am not able to assess the statistics in this study  
 
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
 
Yes - the author's  interpretation is reasonable  
 
 
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically 
sound? If not, can revisions be made to make the work technically sound?  
 
Yes - current version is technically sound  
 
 
PEER REVIEWER COMMENTS:  
 
GEN ERAL COMMENTS: This study is conducted appropriately to determine if the FATZO 
mice fed a western type diet supplemented with fructose is a suitable 0re clinical NASH model. 
The authors have used suitable animal numbers, allocated them randomly to the diff erent 
treatment groups and had someone blinded to the study design perform the histology analysis.  
 
 
REQUESTED REVISIONS:  
 
Authors need to clarify the statistical analysis used here as it is unclear if they used a one way 
ANOVA or a t test. If they used bo th they need to precise in the figure legends which analysis is 
used for which figure.  
 
In addition it is surprising not to see histology data for the liver of the mice on diet for 8and 12 
weeks as they were planned in the study design and blood was used fo r blood chemistry. It 
would be interesting to see the progression of the liver pathology along the full time of the study 
rather than just seeing endpoint.  
 
Finally how can the authors explain that the mice lose fat mass after 4 weeks of diet while their 
body weight steadily increases?  
 
 
ADDITIONAL REQUESTS/SUGGESTIONS:  
 
Get grammatical check as they are some typos in the manuscript  
 
Note: This reviewer report can be downloaded - see attached pdf file.  
 
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 recommend additional statistical review  
 
Quality of written English  
Please indicate th e quality of language in the manuscript:  
 
Needs some language corrections before being publi shed 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
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 shares 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 received reimbursements, fees, funding, or sa lary 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 interests in relation to this paper?  
 
If you can answe r 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.  
 
This reviewer has been re cruited by a partner organization, Research Square. Reviewers with 
declared or apparent competing interests are not utilized for these reviews. This reviewer has 
agreed to publication of their comments online under a Creative Commons Attribution License 
attributed to Research Square and was paid a small honorarium for completing the review within 
a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer 
recommendation.  
 
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 website along with the authors' 
responses. I agree for my report to be m ade 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 named 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:  The FATZO mouse, a next generation model of type 2 diabetes, develops NAFLD and 
NASH when fed a western diet supplemented with fructose  
 
Version: 1 Date: 16 Jan 2019 
 
Reviewer:  Reviewer  2 
 
Reviewer’s report:  
 
PEER REVIEWER ASSESSMENTS:  
 
 
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research 
question(s) (brief or other article types: is there a clear objective)?  
 
Yes - there is a clear objective  
 
 
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for the 
objectiv e? 
 
Yes - the approach is appropriate  
 
 
EXECUTION - Are the experiments and analyses performed with technical rigor to allow 
confidence in the results?  
 
Yes - experiments and analyses were performed appropriately  
 
 
Statistics - Is the use of statistics in the manuscript appropriate?  
 
Not sure - I am not able to assess the statistics in this study  
 
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
 
Yes - the author's  interpretation is reasonable  
 
 
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically 
sound? If not, can revisions be made to make the work technically sound?  
 
Yes - current version is technically sound  
 
 
PEER REVIEWER COMMENTS:  
 
GEN ERAL COMMENTS: This study is conducted appropriately to determine if the FATZO 
mice fed a western type diet supplemented with fructose is a suitable 0re clinical NASH model. 
The authors have used suitable animal numbers, allocated them randomly to the diff erent 
treatment groups and had someone blinded to the study design perform the histology analysis.  
 
 
REQUESTED REVISIONS:  
 
Authors need to clarify the statistical analysis used here as it is unclear if they used a one way 
ANOVA or a t test. If they used bo th they need to precise in the figure legends which analysis is 
used for which figure.  
 
In addition it is surprising not to see histology data for the liver of the mice on diet for 8and 12 
weeks as they were planned in the study design and blood was used fo r blood chemistry. It 
would be interesting to see the progression of the liver pathology along the full time of the study 
rather than just seeing endpoint.  
 
Finally how can the authors explain that the mice lose fat mass after 4 weeks of diet while their 
body weight steadily increases?  
 
 
ADDITIONAL REQUESTS/SUGGESTIONS:  
 
Get grammatical check as they are some typos in the manuscript  
 
Note: This reviewer report can be downloaded - see attached pdf file.  
 
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 recommend additional statistical review  
 
Quality of written English  
Please indicate th e quality of language in the manuscript:  
 
Needs some language corrections before being publi shed 
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
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 shares 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 received reimbursements, fees, funding, or sa lary 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 interests in relation to this paper?  
 
If you can answe r 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.  
 
This reviewer has been re cruited by a partner organization, Research Square. Reviewers with 
declared or apparent competing interests are not utilized for these reviews. This reviewer has 
agreed to publication of their comments online under a Creative Commons Attribution License 
attributed to Research Square and was paid a small honorarium for completing the review within 
a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer 
recommendation.  
 
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 website along with the authors' 
responses. I agree for my report to be m ade 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 named 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