Dear Editor,
We have studied the valuable comments from you, the assistant editor and reviewers carefully, and tried our best to revi the manuscript. The point to point responds to the reviewer’s comments are listed as following:
轮廓是什么意思Responds to the reviewer’s comments:
Reviewer 1
Comment 1: in page 3, line 40, we " changed to rats were
Respon: According to the reviewer’s comment, we have corrected the ntence. Furthermore, we have had the manuscript polished with a professional assistance in writing.
Comment 2: page 25. The style of reference 40 is not right (using initials for the first nam
es). Since this paper has been published, the volume and page Nos should be provided.
Respon: 旅顺Thank you for your careful work. We have added the volume and page numbers for reference 40.
Reviewer 2
Comment电脑远程控制: I would like to thank the authors for their efforts in addressing the criticisms with additional experiments. The one criticism that they did not address was relating to energy expenditure as the reason that the animals on the low calcium diet gained more weight. While I understand that performing this experiment will not affect the conclusion of this manuscript, I do believe that this point could be discusd in the Discussion ction.
Respon: Thank you for your valuable advice. Bad on the previous revision, we further address the relationship between low calcium diet and energy expenditure in the ction of discussion according to your thoughtful comments.
Reviewer 3
Comment 1: In the text you often write: “As previously described”. Unless that paper is from your lab or one of the method paper co-authors is on the prent MS this is not quite proper since the statement infers method development from your lab. There are numerous instances like that in the methods ction; the should all be changed “according to tho described by…..”温暖时光
Respon: We are sorry for this language mistake. We have carefully corrected this phra throughout the manuscript according to your comment.
Comment 2: There are still some wording, ntence structure and grammatical issues even in this basically well put together MS. For example, while authors may have been excited about the data you cannot start a ntence with “Excitedly” in line 418 or “Whatever” in line 395.
Respon: Thank you very much to point out the ntence structure and grammatical iss
ues in our manuscript. According to the comments from you and the editors, we polished the manuscript with a professional assistance in writing, conscientiously.
Comment 3: In my view a big omission in this work is ignoring the anabolic side of lipid metabolism as well as thermogenesis issues. For example all animals consumed the same amount of feed but we had extra fat storage in the low Ca diet groups. So where did the extra energy go Zemel et al (citation 34) in similar work indicate that incread thermogenesis on the high Ca diet explains the dissipation of dietary energy. Further even though Zemel et al (#34) indicated lipogenesis was enhanced in the low Ca diets that was in 2000 and you should have monitored expression of FAS and UCP either as mRNA abundance or actual FAS/UCP changes via proteomics or blotting techniques. In any ca the controls are missing here and not emphasized in the MS. Casual reading of this paper would lead to the conclusion that the dietary Ca effect on fat deposition is strictly a function of incread or decread lipolysis. While lipolysis appears to be a major player, lipogenesis and thermogenesis cannot be ignored for completeness. In Fig 8 you also show a decline
in cAMP for the low Ca diet. Well beta agonists or cAMP enhancers regulate transcription of adipo and liver FAS (in rats (J Biol Chem 271:2307, 1996) and recently with large animal models (Hausman et al J Animal Science 87:1218, 2009 and Haly et al J Animal Science 89: 1011, 2011). In addition cAMP levels could have been monitored.关爱智障儿童 I really do not like the last ntence in the Abstract line 47-50 where you state that “low calcium diet-induced increa in fat mass was due to enhanced lipogenesis mediated by an upregulated CaSR signaling pathway” Your results here show no such thing, this is a completely fal statement bad on data herein. Correct. You show that high Ca diets enhance lipolysis and low Ca diets are antilipolytic. You did not monitor lipid anabolism here at all. See also line 255-257 and lines 333-335 of your MS.
Respon: Thank you for your valuable and thoughtful comments. As you suggested that 胃胀吃什么the anabolic side of lipid metabolism as well as thermogenesis issues should be monitored. We really agree with your viewpoints. In the prent study, we did find that low calcium diet incread the mRNA level of fatty acid syntha (FAS) in white adipo tissue. Furthermore, the FAS mRNA level were also incread in adipocytes after treatme
nt with 1,25-(OH)2D3 in in-vitro experiments. However, the incread FAS mRNA levels were not affected by preventing either the nuclear vitamin D receptor (nVDR) or calcium-nsing receptor (CaSR), suggesting that FAS might not be involved in the CaSR pathway. In addition, we thought that FAS played its role in fatty acid synthesis mainly in liver previously. Besides, the manuscript was required to restrict number of total words and our previous focus was on the antilolytic role of CaSR in the process of fat accumulation. So we ignored to provide the data of FAS mRNA levels in the submitted manuscript. In the newly submitted manuscript, we have provided the mRNA levels according to your helpful suggestion.
农历二十四节气We have reported the effects of dietary calcium on UCP2 mRNA levels in adipo tissue and UCP3 in skeletal muscle in our previous studies (1, 2). Thus, we believed that low calcium diet led to decread thermogenesis in the prent study. It was a pity that we did not measure the rat core temperature in tho studies. The UCP2 mRNA levels in adipocytes were obrved to be decread after treatment of 1,25-(OH)2D3. This effect was prevented by using nVDR CaSR gene silencing but not by CaSR gene knockdown, s
uggesting that UCP2 was not involved in CaSR pathways. In the newly submitted manuscript, we have provided the UCP2 results.
Thank you for your careful reading of our manuscript. We are very sorry for our fault statement in the abstract. We have corrected it in the new manuscript.
让我听见你的声音
