Reviewer’s report
Title: 
Experimental non-alcoholic fatty liver disease causes regional liver
functional deficits as measured by the capacity for galactose metabolism while
whole liver function is preserved
Version: 
1 
Date: 
24 Oct 2022
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 objective?
No - there are minor issues
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?
No - there are issues with the statistics in the 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?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: Experimental non-alcoholic fatty liver disease causes
regional liver functional deficits while total metabolic liver function is preserved
The study aim to investigate in vivo effects of different NAFLD stages on
metabolic liver function, quantified by regional and total hepatic galactose
elimination capacity in a NAFLD model.
Good technique and histopathology
The author present good idea and concept
Scientific writing done well
What need revision is information about sampling, generalize the metabolic
function on the basis of galactose tolerance.
REQUESTED REVISIONS: 
Major comment 
*Information about blood and tissue sampling, its time, methods during early and
late NAFLD and the number in each group to ensure steatosis and galactose
elimination.
Is it at the end 1week and 12 week in the 4 groups (control and NAFLD group),
or blood and tissues sampling after 
galactose injection, so some of the animals
were used for sampling before and after injection and this not match with figure
(1) where the 32 rat used for injection.
*According to table (1) 
liver histology was for 32 rats the whole animal for the
experiment that mean dissection and decapitation of the rats, followed by 
18F-
FDGal injection 
while 
18F-FDGal PET-measurements were for 16 rats, how.
Need clarification.
Also in figure (1) 18F-FDGal injection performed for the whole 32 animals. This
indicated disturbance in group design and sampling. Require revision and
explanation. 
*is there group with 18F-FDGal injection and other without galactose (18F-
alone). 
*The study include 2 factor NAFLD induction and injection of 18F-FDGal , this
require ANOVA 2 way statistical analysis.
*Total metabolic liver function in the title and the whole manuscript should be
changed into regional and total hepatic galactose tolerance.
This because, total metabolic function includes several metabolic functions for
liver include fat (lipolysis cholesterol metabolism and lipogenesis), proteins
(transamination and deamination and protein synthesis), glucose
(gluconeogenesis and glycolysis) and mineral metabolism, so specific function
of galactose tolerance is more suitable scientifically. 
*The proposed title is (Experimental non-alcoholic fatty liver disease causes
regional liver functional deficits while hepatic galactose tolerance is preserved
Material and Methods:
1-Description of diet composition to induce NAFLD should be provided in the
materials. 
2-experimetal schedule for induction of steatosis 
followed by 18F-FDGal
injection should be clear
2- Reference or kits for biochemical analysis should be included in the methods. 
3-Author should offer Age sex and information about laboratory animals 
4-Why author use cholesterol while high carbohydrate is more efficient to
metabolized into fat and more popular to induce steatosis> also cholesterol more
related to cardiovascular disorders. 
5- Page 6 line 21, what is mean by the ……
Results:
Author found, features of non-alcoholic steatohepatitis (NASH), however there
were shortage of data in the result to indicate hepatitis as inflammatory markers
(IL, TNF,…)
*Table (1), data represented as median, however standard deviation or error
should be provided to confirm the significant variations 
Conclusion:
Authors concluded that, In advanced disease stages, the total metabolic liver
function was preserved by the marked growth of fat-free liver mass, this not
supported by data on liver growth (where liver growth requires months and the
experimental time not enough time). The explanation of functional compensation
may be due to changes in glucose, phospholipid and fatty acid metabolism that
may preserve liver function.
ADDITIONAL REQUESTS/SUGGESTIONS: 
*Total metabolic liver function in the title and the whole manuscript should be
changed into regional and total hepatic galactose tolerance. Description of diet
composition to induce NAFLD should be provided in the materials. experimetal
schedule for induction of steatosis 
followed by 18F-FDGal injection should be
clearReference or kits for biochemical analysis should be included in the
methods. Table (1), data represented as median, however standard deviation or
error should be provided to confirm the significant variations
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
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for the benefit of Publons and you as a reviewer, carefully considering the
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find the details of processing in Publons’ privacy policy
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No
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 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 interests 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.
This reviewer has been recruited 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.
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Experimental non-alcoholic fatty liver disease causes regional liver
functional deficits as measured by the capacity for galactose metabolism while
whole liver function is preserved
Version: 
1 
Date: 
24 Oct 2022
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 objective?
No - there are minor issues
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?
No - there are issues with the statistics in the 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?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: Experimental non-alcoholic fatty liver disease causes
regional liver functional deficits while total metabolic liver function is preserved
The study aim to investigate in vivo effects of different NAFLD stages on
metabolic liver function, quantified by regional and total hepatic galactose
elimination capacity in a NAFLD model.
Good technique and histopathology
The author present good idea and concept
Scientific writing done well
What need revision is information about sampling, generalize the metabolic
function on the basis of galactose tolerance.
REQUESTED REVISIONS: 
Major comment 
*Information about blood and tissue sampling, its time, methods during early and
late NAFLD and the number in each group to ensure steatosis and galactose
elimination.
Is it at the end 1week and 12 week in the 4 groups (control and NAFLD group),
or blood and tissues sampling after 
galactose injection, so some of the animals
were used for sampling before and after injection and this not match with figure
(1) where the 32 rat used for injection.
*According to table (1) 
liver histology was for 32 rats the whole animal for the
experiment that mean dissection and decapitation of the rats, followed by 
18F-
FDGal injection 
while 
18F-FDGal PET-measurements were for 16 rats, how.
Need clarification.
Also in figure (1) 18F-FDGal injection performed for the whole 32 animals. This
indicated disturbance in group design and sampling. Require revision and
explanation. 
*is there group with 18F-FDGal injection and other without galactose (18F-
alone). 
*The study include 2 factor NAFLD induction and injection of 18F-FDGal , this
require ANOVA 2 way statistical analysis.
*Total metabolic liver function in the title and the whole manuscript should be
changed into regional and total hepatic galactose tolerance.
This because, total metabolic function includes several metabolic functions for
liver include fat (lipolysis cholesterol metabolism and lipogenesis), proteins
(transamination and deamination and protein synthesis), glucose
(gluconeogenesis and glycolysis) and mineral metabolism, so specific function
of galactose tolerance is more suitable scientifically. 
*The proposed title is (Experimental non-alcoholic fatty liver disease causes
regional liver functional deficits while hepatic galactose tolerance is preserved
Material and Methods:
1-Description of diet composition to induce NAFLD should be provided in the
materials. 
2-experimetal schedule for induction of steatosis 
followed by 18F-FDGal
injection should be clear
2- Reference or kits for biochemical analysis should be included in the methods. 
3-Author should offer Age sex and information about laboratory animals 
4-Why author use cholesterol while high carbohydrate is more efficient to
metabolized into fat and more popular to induce steatosis> also cholesterol more
related to cardiovascular disorders. 
5- Page 6 line 21, what is mean by the ……
Results:
Author found, features of non-alcoholic steatohepatitis (NASH), however there
were shortage of data in the result to indicate hepatitis as inflammatory markers
(IL, TNF,…)
*Table (1), data represented as median, however standard deviation or error
should be provided to confirm the significant variations 
Conclusion:
Authors concluded that, In advanced disease stages, the total metabolic liver
function was preserved by the marked growth of fat-free liver mass, this not
supported by data on liver growth (where liver growth requires months and the
experimental time not enough time). The explanation of functional compensation
may be due to changes in glucose, phospholipid and fatty acid metabolism that
may preserve liver function.
ADDITIONAL REQUESTS/SUGGESTIONS: 
*Total metabolic liver function in the title and the whole manuscript should be
changed into regional and total hepatic galactose tolerance. Description of diet
composition to induce NAFLD should be provided in the materials. experimetal
schedule for induction of steatosis 
followed by 18F-FDGal injection should be
clearReference or kits for biochemical analysis should be included in the
methods. Table (1), data represented as median, however standard deviation or
error should be provided to confirm the significant variations
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
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 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 interests 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.
This reviewer has been recruited 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.
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Experimental non-alcoholic fatty liver disease causes regional liver
functional deficits as measured by the capacity for galactose metabolism while
whole liver function is preserved
Version: 
1 
Date: 
24 Oct 2022
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 objective?
No - there are minor issues
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?
No - there are issues with the statistics in the 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?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: Experimental non-alcoholic fatty liver disease causes
regional liver functional deficits while total metabolic liver function is preserved
The study aim to investigate in vivo effects of different NAFLD stages on
metabolic liver function, quantified by regional and total hepatic galactose
elimination capacity in a NAFLD model.
Good technique and histopathology
The author present good idea and concept
Scientific writing done well
What need revision is information about sampling, generalize the metabolic
function on the basis of galactose tolerance.
REQUESTED REVISIONS: 
Major comment 
*Information about blood and tissue sampling, its time, methods during early and
late NAFLD and the number in each group to ensure steatosis and galactose
elimination.
Is it at the end 1week and 12 week in the 4 groups (control and NAFLD group),
or blood and tissues sampling after 
galactose injection, so some of the animals
were used for sampling before and after injection and this not match with figure
(1) where the 32 rat used for injection.
*According to table (1) 
liver histology was for 32 rats the whole animal for the
experiment that mean dissection and decapitation of the rats, followed by 
18F-
FDGal injection 
while 
18F-FDGal PET-measurements were for 16 rats, how.
Need clarification.
Also in figure (1) 18F-FDGal injection performed for the whole 32 animals. This
indicated disturbance in group design and sampling. Require revision and
explanation. 
*is there group with 18F-FDGal injection and other without galactose (18F-
alone). 
*The study include 2 factor NAFLD induction and injection of 18F-FDGal , this
require ANOVA 2 way statistical analysis.
*Total metabolic liver function in the title and the whole manuscript should be
changed into regional and total hepatic galactose tolerance.
This because, total metabolic function includes several metabolic functions for
liver include fat (lipolysis cholesterol metabolism and lipogenesis), proteins
(transamination and deamination and protein synthesis), glucose
(gluconeogenesis and glycolysis) and mineral metabolism, so specific function
of galactose tolerance is more suitable scientifically. 
*The proposed title is (Experimental non-alcoholic fatty liver disease causes
regional liver functional deficits while hepatic galactose tolerance is preserved
Material and Methods:
1-Description of diet composition to induce NAFLD should be provided in the
materials. 
2-experimetal schedule for induction of steatosis 
followed by 18F-FDGal
injection should be clear
2- Reference or kits for biochemical analysis should be included in the methods. 
3-Author should offer Age sex and information about laboratory animals 
4-Why author use cholesterol while high carbohydrate is more efficient to
metabolized into fat and more popular to induce steatosis> also cholesterol more
related to cardiovascular disorders. 
5- Page 6 line 21, what is mean by the ……
Results:
Author found, features of non-alcoholic steatohepatitis (NASH), however there
were shortage of data in the result to indicate hepatitis as inflammatory markers
(IL, TNF,…)
*Table (1), data represented as median, however standard deviation or error
should be provided to confirm the significant variations 
Conclusion:
Authors concluded that, In advanced disease stages, the total metabolic liver
function was preserved by the marked growth of fat-free liver mass, this not
supported by data on liver growth (where liver growth requires months and the
experimental time not enough time). The explanation of functional compensation
may be due to changes in glucose, phospholipid and fatty acid metabolism that
may preserve liver function.
ADDITIONAL REQUESTS/SUGGESTIONS: 
*Total metabolic liver function in the title and the whole manuscript should be
changed into regional and total hepatic galactose tolerance. Description of diet
composition to induce NAFLD should be provided in the materials. experimetal
schedule for induction of steatosis 
followed by 18F-FDGal injection should be
clearReference or kits for biochemical analysis should be included in the
methods. Table (1), data represented as median, however standard deviation or
error should be provided to confirm the significant variations
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
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 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 interests 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.
This reviewer has been recruited 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.
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant