Sympathetic Innervation of Interscapular Brown Adipose Tissue Is Not a Predominant Mediator of Oxytocin-Induced Brown Adipose Tissue Thermogenesis in Female High Fat Diet-Fed Rats

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have done a commendable job in covering all bases to prove the sympathetic innervation of iBAT and the SNS outflow into iBAT is dispensable for the effects of OT on iBAT temperature, body temperature, food intake and body weight changes. It is also noted that the study is focused on demonstrating the effects OT administration of denervation in female rats and mice in the presence or absence of innervation. The additional studies showing similar conclusions in two different mouse genetic backgrounds add more strength to the soundness of the manuscript. 

The two manuscripts (current and a published manuscript) by this group comprehensively demonstrate that the SNS innervation is not necessary for OT to mediate the protective effects of iBAT. It also poses interesting questions regarding the precise mechanism of action of OT and the effect on the transcriptome and phenotype of iBAT along with other fat pads. The authors have also addressed the possibilities of other organs contributing to the observed effects on iBAT temperature, weight changes and energy intake. 

Author Response

Please see attachment for responses to Reviewer 1.

 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript titled “Sympathetic innervation of interscapular brown adipose tissue 2 is not a predominant mediator of OT-induced BAT thermogenesis in high-fat diet-fed female rats” is interesting, however, I have some comments that would be worth taking up or clarifying in the paper.

·       For example, because experiments were performed in different species, what was the reason?

·       Authors must describe the methodology for obtaining the data (calculations) for the energy intake variable.

·       In methodology, it is important to mention the total number of animals used

·       What is the value of placing a TIBAT graph and another Δ IBAT graph? It is important to justify whether it is worth showing these two figures since it seems that it is the same information only presented in two different ways, and perhaps with Figure 1A the main information can be visualized, the same happens with Figure 2.

·       It is also important to verify how the ΔIBAT was calculated, since the data do not seem to coincide, for example, for the group treated with Vehicle, the ΔIBAT at time 1.25 seems to be less than at time 1, according to figure 1A, however, figure 1B says the opposite, if we analyze other times such as at 4h, the ΔIBAT seems to be greater than at 3h, (in figure 1A) and the opposite is observed in figure 1B. The same can be seen for the groups with 0.1 and 1 mg/kg of beta-3 agonist at different times. Please check.

·       The same situation can be seen at some points in Figure 1D and 1D, for example, in the case of VEH, at 4 hours, are you sure that the ΔIBAT is positive? How was this calculation performed? It was with time "zero", the last point does not seem to be above the basal conditions. Please check carefully.

·       I suggest not using the abbreviation OT in the title, but instead using the full word

·       In the abstract, The authors use some abbreviations, which explain their meaning, however, there are others that they do not, so I suggest homogenizing so that all the abbreviations used are explained, or if possible not using abbreviations in this section, to make reading more fluid. And describe the abbreviations in the body of the manuscript.

·       On line 1, there is a phrase highlighted in bold, is this correct or is it an error?

·       Some definitions of some abbreviations such as IBAT, EWAT, IBAT do not appear in the text

·       On line 36, is it 16.1 mg/day or 16.1 micrograms/day?

·       On line 188 enrofloxacin is in a different font size

·       Authors should homogenize the way of expressing some variables, for example, sometimes they use T_IBAT and other times TIBAT, in text and figures

·       what is the meaning of “†0.05<P<0.1”?, in the statistical analysis section the authors do not explain that it will be used.

·       the symbology †0.05<P<0.1 is not used in any figure 1, so it is not necessary to express it in the description, apart from in their statistical analysis section they mention that they will consider a statistically significant difference from p<0.05, and here the authors put a symbol to show a difference when it is less than 0.1?

 

·       There is a typographical error in the units of 0.5 on line 446., figure legend 3.

Author Response

Please see attachment for responses to Reviewer 2.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have responded and made the necessary adjustments based on the comments. In that regard, I believe the criteria for publication have been met. My current concern is the level of similarity detected with iThenticate, which stands at 48%. While some short phrases, names, affiliations, or general descriptions are marked, my main worry is that there are almost entire paragraphs or descriptions, particularly in the results and discussion sections, that should be unique but show a high percentage of similarity with other works. This aspect should be addressed before publication

Comments for author File: Comments.pdf

Author Response

Please see attachment

Author Response File: Author Response.pdf

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

I have reviewed the new version of the manuscript and have no further comments. I consider that the authors have made the appropriate adjustments.

Author Response

Please see attached.

Author Response File: Author Response.pdf