Mirabegron and Physical Exercise Is a Potential Strategical for BAT Activation in Obesity

Round 1

Reviewer 1 Report

Comments for author File: Comments.pdf

Author Response

 

Firstly, we would like to thank you for the opportunity to revise our paper. We have read the comments and judged the suggestions very appropriately.We hope our efforts are evident from the responses below and the revised manuscript. All changes in the current document are highlighted in yellow. 

Author Response File: Author Response.docx

Reviewer 2 Report

In this article, Antunes et al. review the role of a β(3)-adrenoceptor agonist called Mirabegron and its potential as a supplemental strategy with physical exercise for countering obesity. It's a timely review as obesity is increasing exponentially due to lifestyle changes. The review covers important topics; however, the authors need to address a few gaps and concerns to make this article acceptable.

 

1. The major concerns about the article at this point are the novelty and completeness of the article. A recent review by Bel et al., 2021 (PMID: 33650753) discusses the same topic with similar studies. The authors need to revise their article to include enough new literature and topics so that it differs from the previous publication. Regarding completeness, the authors have covered important topics but need to be more comprehensive. I have specified what needs to be added to the upcoming concerns.
2. The studies reviewed by the authors are primarily association-based. The authors need to provide details about the mechanism by which Mirabegron promotes the beiging of the Adipose Tissues. A supporting figure would be useful as well.
3. Obesity involves a complex interaction of different metabolic organs and immune cells. The authors need separate sections addressing the following topics with relevant in vitro and in vivo studies:
1. What is the impact of Mirabegron on immune cell states?
2. What is the impact of Mirabegron on pancreas, kidney, and liver function? Is it improved? (This is not from a toxicity perspective but from the mechanistic and organ function perspective)
4. In the introduction (or a separate section), a brief background on obesity pathogenesis with a large focus on WATs and BATs for the reader's understanding before you get into the Mirabegron is warranted.
5. A section on the molecular signaling mechanism of Mirabegron is necessary.
6. The effect of cold is an additional major factor that plays a role in beiging. Does Mira act similarly in terms of mechanism? Does Mira work synergistically in exposure to cold?
7. Does/can Mira affect Irisin levels?

 

Minor concerns:

 

1. In the abstract, the authors say, "According to the results of this review" – Instead, they should edit it to 'According to the results of the studies presented in this review."
2. In the introduction, "Interventions like nutritional approaches and the practice of physical exercise are potential therapies to combat obesity; however, in some cases, these are not sufficient." The authors need to complete this thought by explaining why it is not sufficient.
3. In section 3, the authors suggest, "Thus, a high lipid content meal could be interesting for mirabegron administration." They also need to comment on the risk of obesity if individuals consume high lipid-content meals.

Author Response

Firstly, we would like to thank you for the opportunity to revise our paper. We have read the comments and judged the suggestions very appropriately.We hope our efforts are evident from the responses below and the revised manuscript. All changes in the current document are highlighted in yellow. 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments for author File: Comments.pdf

Author Response

 

Firstly, we would like to thank you for the opportunity to revise our paper. We have read the reviewer's comments and judged the suggestions very appropriately. We are confident that the edits within this revision have satisfied the reviewer's concerns and have significantly improved the manuscript. We hope our efforts are evident from the responses below and the revised manuscript. All changes in the current document are highlighted in yellow. Also, we have provided a point-by-point commentary for the reviewer’s comments.

Author Response File: Author Response.docx

Reviewer 2 Report

The authors have done a fine job addressing most of my concerns. The manuscript can be accepted in its present form.

Author Response

 

Firstly, we would like to thank you for the opportunity to revise our paper. We have read the reviewer's comments and judged the suggestions very appropriately. We are confident that the edits within this revision have satisfied the reviewer's concerns and have significantly improved the manuscript. We hope our efforts are evident from the responses below and the revised manuscript. All changes in the current document are highlighted in yellow. Also, we have provided a point-by-point commentary for the reviewer’s comments. 

 

Author Response File: Author Response.docx