Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults
Version: 2 Date: 04 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The introduction is strong but could benefit from a more explicit definition of relative fat
mass (RFM) in the context of this study. You mention that it is a measure of obesity but could
emphasize more why RFM is a better predictor compared to BMI, especially for understanding
fat distribution, which may be more relevant to gallstone formation.
-The discussion of gallstone risk factors could be expanded slightly. While you list common risk
factors (e.g., obesity, metabolic syndrome, etc.), it would be helpful to include a brief overview
of the pathophysiology behind gallstone formation to provide more context as to why RFM
might be linked to the disease.
-The exclusion criteria are mentioned but not explained in detail in the text. You refer to "Fig.
1," but ensure that this figure is properly described in the text or supplemented with more
information in the methods section.
-While the measurement of RFM is described, it might help to provide more context about the
formula’s validity or its adoption in previous research, especially when introducing it as a more
accurate measure than BMI. A brief comparison of RFM’s reliability in other studies would add
credibility to its use here.
-While you mention that this is the first thorough examination of the relationship between
RFM and gallstones, it might be helpful to briefly reintroduce RFM’s definition in this section,
especially for readers who may not be familiar with the term. You described its role in predicting
obesity-related health outcomes earlier, but reiterating why RFM is a better measure than BMI
in this context would help reinforce the novelty and importance of your findings.
-The explanation of how obesity contributes to gallstone formation is strong but could benefit
from additional references or a deeper dive into the molecular mechanisms. For example, you
mention the increased activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its
role in cholesterol production. Expanding on how this ties directly to the supersaturation of bile
or other biochemical processes leading to stone formation would strengthen the mechanistic
argument.
-When discussing the stronger association between RFM and gallstones in younger adults and
females, consider adding a bit more explanation as to why this might be the case. For example,
you could explore the hormonal factors or differences in fat distribution between males and
females that may make women more susceptible to gallstones at certain stages of life.
Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults
Version: 2 Date: 04 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The introduction is strong but could benefit from a more explicit definition of relative fat
mass (RFM) in the context of this study. You mention that it is a measure of obesity but could
emphasize more why RFM is a better predictor compared to BMI, especially for understanding
fat distribution, which may be more relevant to gallstone formation.
-The discussion of gallstone risk factors could be expanded slightly. While you list common risk
factors (e.g., obesity, metabolic syndrome, etc.), it would be helpful to include a brief overview
of the pathophysiology behind gallstone formation to provide more context as to why RFM
might be linked to the disease.
-The exclusion criteria are mentioned but not explained in detail in the text. You refer to "Fig.
1," but ensure that this figure is properly described in the text or supplemented with more
information in the methods section.
-While the measurement of RFM is described, it might help to provide more context about the
formula’s validity or its adoption in previous research, especially when introducing it as a more
accurate measure than BMI. A brief comparison of RFM’s reliability in other studies would add
credibility to its use here.
-While you mention that this is the first thorough examination of the relationship between
RFM and gallstones, it might be helpful to briefly reintroduce RFM’s definition in this section,
especially for readers who may not be familiar with the term. You described its role in predicting
obesity-related health outcomes earlier, but reiterating why RFM is a better measure than BMI
in this context would help reinforce the novelty and importance of your findings.
-The explanation of how obesity contributes to gallstone formation is strong but could benefit
from additional references or a deeper dive into the molecular mechanisms. For example, you
mention the increased activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its
role in cholesterol production. Expanding on how this ties directly to the supersaturation of bile
or other biochemical processes leading to stone formation would strengthen the mechanistic
argument.
-When discussing the stronger association between RFM and gallstones in younger adults and
females, consider adding a bit more explanation as to why this might be the case. For example,
you could explore the hormonal factors or differences in fat distribution between males and
females that may make women more susceptible to gallstones at certain stages of life.
Please review this paper.
user
Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults
Version: 2 Date: 04 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The introduction is strong but could benefit from a more explicit definition of relative fat
mass (RFM) in the context of this study. You mention that it is a measure of obesity but could
emphasize more why RFM is a better predictor compared to BMI, especially for understanding
fat distribution, which may be more relevant to gallstone formation.
-The discussion of gallstone risk factors could be expanded slightly. While you list common risk
factors (e.g., obesity, metabolic syndrome, etc.), it would be helpful to include a brief overview
of the pathophysiology behind gallstone formation to provide more context as to why RFM
might be linked to the disease.
-The exclusion criteria are mentioned but not explained in detail in the text. You refer to "Fig.
1," but ensure that this figure is properly described in the text or supplemented with more
information in the methods section.
-While the measurement of RFM is described, it might help to provide more context about the
formula’s validity or its adoption in previous research, especially when introducing it as a more
accurate measure than BMI. A brief comparison of RFM’s reliability in other studies would add
credibility to its use here.
-While you mention that this is the first thorough examination of the relationship between
RFM and gallstones, it might be helpful to briefly reintroduce RFM’s definition in this section,
especially for readers who may not be familiar with the term. You described its role in predicting
obesity-related health outcomes earlier, but reiterating why RFM is a better measure than BMI
in this context would help reinforce the novelty and importance of your findings.
-The explanation of how obesity contributes to gallstone formation is strong but could benefit
from additional references or a deeper dive into the molecular mechanisms. For example, you
mention the increased activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its
role in cholesterol production. Expanding on how this ties directly to the supersaturation of bile
or other biochemical processes leading to stone formation would strengthen the mechanistic
argument.
-When discussing the stronger association between RFM and gallstones in younger adults and
females, consider adding a bit more explanation as to why this might be the case. For example,
you could explore the hormonal factors or differences in fat distribution between males and
females that may make women more susceptible to gallstones at certain stages of life.
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