The Beige Adipocyte as a Therapy for Metabolic Diseases
Round 1
Reviewer 1 Report
Adipose tissue has proven to serve as an abundant, accessible and rich source of adult stem cells with multipotent properties suitable for tissue engineering and regenerative medical applications. There has been increased interest in adipose-derived stem cells (ASCs) for tissue engineering applications, and not only.
I suggest that authors should expand this aspect concerning APCs, being very important.
Furthermore, authors should stress the potential impact of beige adipocyte thermogenesis on systemic metabolism that is not yet clear and an understanding of beige adipocyte development and regulation is also limited. Biology (Basel)2019 Jul 31;8(3).Beige Fat, Adaptive Thermogenesis, and Its Regulation by Exercise and Thyroid Hormone.
Finally, thyroid hormones also exert impacts on metabolic rate via effects on brown adipocytes which express type 2 deiodinase. Knocking out DIO2 makes mice cold intolerant, this is a key point to stress as evident in...Mol Aspects med.2019 Aug;68:60-73. Switching on the furnace: Regulation of heat production in brown adipose tissue.
Author Response
Reviewer. 1.
Adipose tissue has proven to serve as an abundant, accessible and rich source of adult stem cells with multipotent properties suitable for tissue engineering and regenerative medical applications. There has been increased interest in adipose-derived stem cells (ASCs) for tissue engineering applications, and not only.
response: We added some new knowledge about ADMSC
1- I suggest that authors should expand this aspect concerning APCs, being very important
response: OK, I was added
2- Furthermore, authors should stress the potential impact of beige adipocyte thermogenesis on systemic metabolism that is not yet clear, and an understanding of beige adipocyte development and regulation is also limited.
response: OK
3- Biology (Basel)2019 Jul 31;8(3). Beige Fat, Adaptive Thermogenesis, and Its Regulation by Exercise and Thyroid Hormone.
response: OK, it was added.
4- Finally, thyroid hormones also exert impacts on metabolic rate via effects on
brown adipocytes which express type 2 deiodinase. Knocking out DIO2 makes mice cold intolerant, this is a key point to stress as evident in...Mol Aspects med.2019 Aug;68:60-73. Switching on the furnace: Regulation of heat production in brown adipose tissue.
response: OK, it was added.
Reviewer 2 Report
The topic of this interview is important and interesting; however, language should be improved. The text is occasionally unclear, and the grammar is occasionally incorrect. It does not meet yet the standards of an internationally-circulated journal.
In general, beige cell metabolism is barely discussed in this review, despite its clinical relevance to increase energy expenditure. The authors should discuss different aspects of energy expenditure, how they are triggered and can be targeted. Metabolic pathways like beta-oxidation, creatine metabolism and calcium-dependent metabolism.
The authors should distinguish between studies in mice and in humans, if exist, throughout the text.
Title – “Development Beige Adipocyte a therapy for Metabolic Diseases” -> “The Beige Adipocyte as a therapy for the Metabolic Syndrome”
Line 24 – beige adipocytes can form from mesenchymal stem cells or from conversion of white adipocytes. Please emit the incorrect term “mesenchymal adipose cells”.
Line 28 – “great” -> “unique”
Table 1. – Add “Norepinephrine” to the induction signals. IL-6 – the “6” fell into the next line. “FAB4” -> “FABP4 (aP2)”. Add the marker “UCP1” to both brown and beige cells.
Beige adipocytes can also originate in SMA+/PPARg+ mural adipose progenitors.
Lines 144-145 – methylation changes – increases or decreases? And not only in muscle, but also in the adipose tissue and hypothalamus.
Line 157 -> Epigenetics and mechanisms of chromatin modification
Line 181 – deletion of this gene. Which gene? EHMT1 or UCP1?
Line 202 - “adipocytes Beige” -> “beige adipocytes”
Line 204 - “the macrophage type 2” -> “type 2 macrophages”
Line 207-8 - “Adipose tissue macrophage 2” -> “Adipose tissue type 2 macrophage”
Line 256 – with “stimulation” or “activation” of the immune system?
Induction of beige adipocytes by cold – findings regarding the involvement of the sympathetic nervous system are missing. For example, adrenergic receptors.
Physical exercise, missing info – involvement of UCPs in muscle cells… Fatty acid oxidation in beige cells due to physical exercise may be involved in thermogenesis and feed-forward of beiging…
Line 302-303 – Is IL-6 secreted from muscle cells?
Lines 326-327 – what is the source of these endocrine factors?
Please also check the literature on contradicting effects by estrogen receptor inhibition – which can also induce beiging under certain circumstances.
The section on potential therapeutics is not bad, bringing up a useful point of view.
Author Response
Reviewer. 2.
The topic of this interview is important and interesting; however, language should be improved. The text is occasionally unclear, and the grammar is occasionally incorrect. It does not meet yet the standards of an internationally circulated journal.
In general, beige cell metabolism is barely discussed in this review, despite its clinical relevance to increase energy expenditure.
a- The authors should discuss different aspects of energy expenditure, how they are triggered and can be targeted. Metabolic pathways like beta-oxidation, creatine metabolism and calcium-dependent metabolism.
response: It was added.
The authors should distinguish between studies in mice and in humans, if exist,
throughout the text.
response: OK
Title – “Development Beige Adipocyte a therapy for Metabolic Diseases” -> “The
Beige Adipocyte as a therapy for the Metabolic Syndrome”
response:OK , was changed
Line 24 – beige adipocytes can form from mesenchymal stem cells or from conversion of white adipocytes. Please emit the incorrect term “mesenchymal adipose cells”.
response:OK , was changed
Line 28 – “great” -> “unique” OK ,
response:it was changed
Table 1. – Add “Norepinephrine” to the induction signals. IL-6 – the “6” fell into the next line. “FAB4” -> “FABP4 (aP2)”. Add the marker “UCP1” to both brown and beige cells.
response:OK , it was changed
Beige adipocytes can also originate in SMA+/PPARg+ mural adipose progenitors.
response:It was added.
Lines 144-145 – methylation changes – increases or decreases? And not only in muscle, but also in the adipose tissue and hypothalamus.
response:Methylation increase
Line 157 -> Epigenetics and mechanisms of chromatin modification.
response:It was changed
Line 181 – deletion of this gene. Which gene? EHMT1 or UCP1?.
response:EHMT1
Line 202 - “adipocytes Beige” -> “beige adipocytes”
response:it was changed
Line 204 - “the macrophage type 2” -> “type 2 macrophages”
response: it was changed
Line 207-8 - “Adipose tissue macrophage 2” -> “Adipose tissue type 2 macrophage” it
response:was changed
Line 256 – with “stimulation” or “activation” of the immune system?
response:activation
Induction of beige adipocytes by cold – findings regarding the involvement of the sympathetic nervous system are missing. For example, adrenergic receptors.
Physical exercise, missing info – involvement of UCPs in muscle cells… Fatty acid
oxidation in beige cells due to physical exercise may be involved in thermogenesis and feed-forward
of beiging…
response:it was added
Round 2
Reviewer 2 Report
No comments.