To increase transparency, PeerJ operates a system of 'optional signed reviews and history'. This takes two forms: (1) peer reviewers are encouraged, but not required, to provide their names (if they do so, then their profile page records the articles they have reviewed), and (2) authors are given the option of reproducing their entire peer review history alongside their published article (in which case the complete peer review process is provided, including revisions, rebuttal letters and editor decision letters).
The authors have carefully addressed reviewers question and revised the manuscript according by adding new data and discussion. This work is important to show that a CMKLR1 agonist might improve glucose homeostasis by increasing insulin-stimulated glucose uptake by adipocytes and would be of benefit in the treatment of type 2 diabetes associated with obesity.
Both reviewers feel this work is of interest, however, more explanation on the "chemerin pathway" and a concise presentation are desired.
It is important to perform the following experiments.
1. Compare the plasma chemerin level in wild-type, CMKLR1 knockout, and heterozygote mice.
2. Determine whether murine chemerin and some C-terminal peptides would decrease the high fat diet-induced obesity as well as glucose intolerance, through CMKLR1 or not.
Without showing the data mentioned above, the conclusion of this study is remarkably weakened. Please consider to supplement the manuscript with these data.
This study addresses an interesting and important question. Knockout mouse models used in this study are valuable. The authors are encouraged to provide more explanation and insights on the regulation of the "chemerin pathway" therapeutically. Specifically, is it on the level of agonists or the expression of chemerin receptor?
Experimental designed include too many conditions with superficial observation, which made this study without a clear focus and deep mechanistic insight.
There were hug data, but the associations of chemerin with studied conditions were not very excited since almost of measurements were mildly changed.
All text and materials provided via this peer-review history page are made available under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.