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Review
Peer-Review Record

Epigenetic Regulators of White Adipocyte Browning

by Ravikanth Nanduri
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Submission received: 1 November 2020 / Revised: 16 December 2020 / Accepted: 6 January 2021 / Published: 12 January 2021

Round 1

Reviewer 1 Report

In the current review by Nanduri, R covered an important topic in the field of metabolism regarding epigenetic regulation.  The review is really well written and structured with excellent illustrations summarizing the findings. The most recent advances in the field are nicely discussed providing an excellent overview for the readers.

Author Response

In the current review by Nanduri, R covered an important topic in the field of metabolism regarding epigenetic regulation.  The review is really well written and structured with excellent illustrations summarizing the findings. The most recent advances in the field are nicely discussed providing an excellent overview for the readers.

Response: We would like to thank the reviewer for evaluating the manuscript and also for appreciating our efforts.

Reviewer 2 Report

Understanding regulatory mechanisms and key players of adipogenesis and adipocyte functions are indeed very important given the therapeutic potential of adipose tissue. And especially a review of epigenetic regulators and transcription factors is very useful. The author classified those players into distinct groups: HAT, HDAC, HMT, Histone demethylase, DNA Methyltransferases and demethylases, transcription factors, and miRNAs, and described reported functions.

However, this manuscript is not well organized and novelty is not significant enough beyond minor updates of recent discoveries. Overall, this manuscript simply lists up key regulators and add a one- or two-sentence summary of the reference. It would be more informative and have more novelty if it focuses on more specialized topics.

Also, importantly, adipocyte often displays similar or different phenomena/key regulators between mouse and human. But the author did not specifically distinguish them. Yet the cases of gene symbols are not consistent in the figures and throughout the manuscripts.

Minor points:

  • Table 1 is a simple summary of what they already wrote in the text. not required.
  • In the abstract,
    • can we say that browning is "trans differentiation"?
    • "brown like" -> "brown-like"
    • "Brown fat cells require activation" -> activation for what?
  • Sentences out of context without a smooth connection.
    • In the abstract, "Also, adult humans have little or no active BAT" What is this sentence for?
    • In the abstract, "The evidence of induction of beige adipocytes by simple intermittent fasting highlighted the importance of beige adipocytes in improving humans' metabolic health." How does it mean "importance of beige adipocyte"?
    • In the abstract, "This literature review is a comprehensive and focused update on epigenetic regulators vital for white and beige adipogenesis." Is this about browning? or beige adipogenesis? or both? The title only says "browning".
    • page 2 line 6: "without affecting the DNA sequence" not required.
    • "The usage of the β-AR agonists for the therapeutic purpose in treating dyslipidemia and obesity is still in question with the associated side effects [13, 14]." No logical connection with the previous and the next sentence.
  • Typos
    • page 2 line 6: involves
    • page 2 line 9: thermogenic

Author Response

Understanding regulatory mechanisms and key players of adipogenesis and adipocyte functions are indeed very important given the therapeutic potential of adipose tissue. And especially a review of epigenetic regulators and transcription factors is very useful. The author classified those players into distinct groups: HAT, HDAC, HMT, Histone demethylase, DNA Methyltransferases and demethylases, transcription factors, and miRNAs, and described reported functions.

However, this manuscript is not well organized and novelty is not significant enough beyond minor updates of recent discoveries. Overall, this manuscript simply lists up key regulators and add a one- or two-sentence summary of the reference. It would be more informative and have more novelty if it focuses on more specialized topics. Also, importantly, adipocyte often displays similar or different phenomena/key regulators between mouse and human. But the author did not specifically distinguish them. Yet the cases of gene symbols are not consistent in the figures and throughout the manuscripts.

Response: We would like to thank the reviewer for their time and efforts and also for providing valuable comments to improve the manuscript. We made a sincere effort to improve the novelty of our review by incorporating more literature, provided more text on each regulator wherever available, and also added a summary to each section of the review. We also edited the manuscript to bring consistency in gene symbols. This review includes most of the literature based on mouse models or cell lines, with some correlation to humans. Hence, we could not distinguish between mouse and human. We believe this first of its kind review and is a point of reference for all the epigenetic regulators that regulate white adipocyte identity or white adipocyte browning. We have also incorporated figure 3 to bring novelty. 

 

Minor points:

  • Table 1 is a simple summary of what they already wrote in the text. not required.

Response: We have edited this table to provide a single point conclusion for its role in adipogenesis. We feel this table is important and hope the reviewer now agrees for keeping it in the review.

  • In the abstract,
    • can we say that browning is "transdifferentiation"?
  • Response: Cell identity is defined by enhancers. WAT browning results in the formation of brown specific enhancers in white adipocytes. Same time Beta-Adrenergic agonist treatment can induce UCP1 in mature white adipocytes also. Hence, we feel it is right to mention it as transdifferentiation.
  • "brown like" -> "brown-like"

Response: Authors agreed. Corrected throughout the manuscript.

  • "Brown fat cells require activation" -> activation for what?

Response: Brown fat requires activation to protect against hypothermia. Edited the manuscript as suggested.

  • Sentences out of context without a smooth connection.
    • In the abstract, "Also, adult humans have little or no active BAT" What is this sentence for?

Response: Removed from the abstract.

  • In the abstract, "The evidence of induction of beige adipocytes by simple intermittent fasting highlighted the importance of beige adipocytes in improving humans' metabolic health." How does it mean "importance of beige adipocyte"?

Response: Removed from the abstract.

  • In the abstract, "This literature review is a comprehensive and focused update on epigenetic regulators vital for white and beige adipogenesis." Is this about browning? or beige adipogenesis? or both? The title only says "browning".

Response: This is review is all about white adipocytes and their browning into brown-like beige adipocytes. Hence, edited the title also as “Epigenetic regulators of white adipocyte browning”

  • page 2 line 6: "without affecting the DNA sequence" not required.

             Response: Removed the line as suggested

  • "The usage of the β-AR agonists for the therapeutic purpose in treating dyslipidemia and obesity is still in question with the associated side effects [13, 14]." No logical connection between the previous and the next sentence.

Response: Authors agreed. Edited the abstract to bring the connection.

  • Typos
    • page 2 line 6: involves
    • page 2 line 9: thermogenic

Response: Corrected as suggested.

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