Oxytocin’s Regulation of Thermogenesis May Be the Link to Prader–Willi Syndrome

Round 1

Reviewer 1 Report

The manuscript “Oxytocin’s Regulation of Thermogenesis May Be the Explanation of Prader-Willi Syndrome” by Claudia Camerino is an interesting review of oxytocin knowledge with some hypotheses regarding PWS origin. However, there are some areas that needs to be reconsidered.

In my opinion the main thesis is still a hypothesis, therefore it should be presented with more consideration. We are aware of the complexity of PWS, still not fully understood role of many genes involved and hypotheses of hypothalamic origin of the disease. Yet it does not refer only to the oxytocin function.

I would recommend reconsider the title and the text, especially the conclusion. Moreover, the conclusion sounds more like a part of the discussion.

Please see below more specific comments:

1. Line 12: “is characterized by intellectual disability”. I would be careful with such a definitive statement. It is just a part of PWS clinical picture, not always the main one. As the Author mention below it is rather “mild cognitive disability” (line 36).

2. Line 22-23: please avoid the repeated information “This review will describe the update on PWS and the recent discoveries on Oxytocin regulation of thermogenesis together with the potential link between Oxytocin regulation of thermogenesis and PWS to create a new groundwork for the treatment of this condition.”

3. Line 356: “PWS is caused by an Oxt’s dysfunction.” It is still one of the hypothesis and surely not the only reason, as mentioned below: “The question arises if Prader-Willi Syndrome is the Oxytocin’s disease” (line 412).

Minor editing of English language required

Author Response

Reviewer #1.

The manuscript “Oxytocin’s Regulation of Thermogenesis May Be the Explanation of Prader-Willi Syndrome” by Claudia Camerino is an interesting review of oxytocin knowledge with some hypotheses regarding PWS origin. However, there are some areas that needs to be reconsidered.

In my opinion the main thesis is still a hypothesis, therefore it should be presented with more consideration. We are aware of the complexity of PWS, still not fully understood role of many genes involved and hypotheses of hypothalamic origin of the disease. Yet it does not refer only to the oxytocin function.

I would recommend reconsider the title and the text, especially the conclusion. Moreover, the conclusion sounds more like a part of the discussion.

Respected reviewer #1 the title has been changed and the old conclusion has been moved to a new chapter titled “Future directions” while a new conclusion with no references has been added.

Please see below more specific comments:

1. Line 12: “is characterized by intellectual disability”. I would be careful with such a definitive statement. It is just a part of PWS clinical picture, not always the main one. As the Author mention below it is rather “mild cognitive disability” (line 36). Line 12 has been changed in “cognitive impairment”.
2. Line 22-23: please avoid the repeated information “This review will describe the update on PWS and the recent discoveries on Oxytocin regulation of thermogenesis together with the potential link between Oxytocin regulation of thermogenesis and PWS to create a new groundwork for the treatment of this condition.” This sentence has been rewritten in the introduction line.
3. Line 356: “PWS is caused by an Oxt’s dysfunction.” It is still one of the hypothesis and surely not the only reason, as mentioned below: “The question arises if Prader-Willi Syndrome is the Oxytocin’s disease” (line 412). Line 356 has been changed accordingly.

Comments on the Quality of English Language

Minor editing of English language required.

Done

Author Response File: Author Response.pdf

Reviewer 2 Report

Although the manuscript is written clearly and well organized, some modifications are recommended. Namely, given the fact that it is not sure if Prader-Willi Syndrome is the Oxytocin’s disease and since this is still a hypotheses (i.e. the lack of positive results from clinical trials) it should be careful with some statements, i.e. „PWS is caused by an Oxt’s dysfunction.“ Also, the Conclusion section needs to be shortened with the main conclusions regarding this Review, without references provided.

Author Response

Reviewer #2.

Although the manuscript is written clearly and well organized, some modifications are recommended. Namely, given the fact that it is not sure if Prader-Willi Syndrome is the Oxytocin’s disease and since this is still a hypotheses (i.e. the lack of positive results from clinical trials) it should be careful with some statements, i.e. „PWS is caused by an Oxt’s dysfunction.“ Also, the Conclusion section needs to be shortened with the main conclusions regarding this Review, without references provided.

Respected reviewer #2.

The sentence the lack of positive results from clinical trials has been changed in  “the lack of consistency in the existing clinical trials”.

The sentence “PWS is caused by an Oxt’s dysfunction” has been changed in “the Oxt system in PWS appears dysfunctional”.

The old conclusion has been moved to a new chapter titled “Future directions” while a new conclusion with no references has been added.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Dear Author,

Thank you for accepting the suggestions for improvement of the manuscript.

I have one comment regarding the Conclusion: Lines 443-445: “Oxt’s regulation of thermogenesis and Oxt-driven muscle contraction are well related especially in the manifestation of PWS (Figure.1) as thermoregulation switch-on Oxt gene in PVN that increase Oxtr expression and decreases circulating Oxt while triggering muscle contraction.”

I would recommend removing the second part of the sentence, together with a reference to Fig 1, as it is too detailed for Conclusions and it was mentioned in the Discussion.

Comments for author File: Comments.pdf

-