Title: Comparative Effects of Aerobic and Resistance Exercise on Bile Acid Profiles and Liver
Function in Patients with Non-Alcoholic Fatty Liver Disease
Version: 2 Date: 08 Feb 2025
Reviewer:  Ayoub Saeidi
Reviewer's report:
1- In the results section, it is mentioned that there are significant reductions in body shape
parameters (weight, BMI, PBF, WHR) after exercise. However, please provide more statistical
details such as p-values, effect sizes, and confidence intervals for these findings. This will add
rigor to your claims and allow readers to assess the strength of the effects more clearly.
2- While the paper suggests that aerobic exercise improves liver function through bile acid
metabolism, particularly through UDCA, a deeper discussion on the underlying molecular
mechanisms would strengthen the scientific depth of the manuscript. Specifically, please explain
how UDCA and other bile acids impact liver cells on a cellular and molecular level.
3- The combined exercise (aerobic + resistance) group did not show the expected benefits
compared to the aerobic group. It would be valuable to discuss why this combination did not
yield superior results. Could the reduced duration of aerobic exercise in this group have caused
suboptimal results? Are there any physiological mechanisms that may explain why combining
the two types of exercise negates the benefits observed with aerobic exercise alone?
4- It is not clear how adherence to the exercise protocols was monitored. Please clarify whether
any measures were taken to ensure that participants adhered to their assigned exercise regimens.
Additionally, it would be helpful to address whether other confounding factors (e.g., diet, sleep,
stress) were controlled for or monitored during the study, as these could influence liver function
and metabolic parameters.
5- Some sentences in the manuscript are long and complex, which may hinder clarity. For
instance, the sentence “Notably, some parameters that changed in the AT group no longer
showed significant differences in the AT + RT group, possibly due to the reduced duration of
aerobic activity in the combined exercise regimen…” could be simplified. Please review the text
and break up complex sentences to improve readability.
6- While the study finds that aerobic exercise increases specific bile acid levels (e.g., UDCA,
TUDCA, TCA), further discussion on the roles of these bile acids in liver function would
enhance the manuscript. For example, why does UDCA specifically benefit hepatocytes? What
is the role of TUDCA, TCA, and other conjugated bile acids in improving liver health, and how
does aerobic exercise influence these pathways?
7- While the study provides valuable insights into exercise regimens for young individuals with
NAFLD, it primarily focuses on a specific demographic (young adults). Please address how
these findings might be generalized to other populations, such as older adults or those with
more severe NAFLD. Additionally, consider the limitations of using a short-term (8-week)
intervention period and discuss the need for longer follow-up studies to assess the sustainability
of these benefits.
8- The study provides exercise protocols for both aerobic and resistance training but lacks
detailed information on how intensity and duration were tailored for each participant. For
example, while the aerobic exercise intensity was set to 50%-70% of maximum heart rate,
the intensity for resistance training is not clearly defined. Please provide more details on how
exercise intensity was adjusted for individual participants in both modalities and clarify how it
was monitored throughout the study.
9- Please reference the following articles in the text:
#  High-intensity Interval Training Improves Lipocalin-2 and Omentin-1 Levels in Men with
Obesity
# Differential Effects of Exercise Programs on Neuregulin 4, Body Composition and
Cardiometabolic Risk Factors in Men With Obesity
# Intensity Dependent Effects of Interval Resistance Training on Myokines and Cardiovascular
Risk Factors in Males With Obesity
# Intense circuit resistance training along with Zataria multiflora supplementation reduced
plasma retinol binding protein-4 and tumor necrosis factor-alpha in postmenopausal females
# Effects of Exercise Training on Bone Health Parameters in Individuals With Obesity: A
Systematic Review and Meta-Analysis
Title: Comparative Effects of Aerobic and Resistance Exercise on Bile Acid Profiles and Liver
Function in Patients with Non-Alcoholic Fatty Liver Disease
Version: 2 Date: 08 Feb 2025
Reviewer:  Ayoub Saeidi
Reviewer's report:
1- In the results section, it is mentioned that there are significant reductions in body shape
parameters (weight, BMI, PBF, WHR) after exercise. However, please provide more statistical
details such as p-values, effect sizes, and confidence intervals for these findings. This will add
rigor to your claims and allow readers to assess the strength of the effects more clearly.
2- While the paper suggests that aerobic exercise improves liver function through bile acid
metabolism, particularly through UDCA, a deeper discussion on the underlying molecular
mechanisms would strengthen the scientific depth of the manuscript. Specifically, please explain
how UDCA and other bile acids impact liver cells on a cellular and molecular level.
3- The combined exercise (aerobic + resistance) group did not show the expected benefits
compared to the aerobic group. It would be valuable to discuss why this combination did not
yield superior results. Could the reduced duration of aerobic exercise in this group have caused
suboptimal results? Are there any physiological mechanisms that may explain why combining
the two types of exercise negates the benefits observed with aerobic exercise alone?
4- It is not clear how adherence to the exercise protocols was monitored. Please clarify whether
any measures were taken to ensure that participants adhered to their assigned exercise regimens.
Additionally, it would be helpful to address whether other confounding factors (e.g., diet, sleep,
stress) were controlled for or monitored during the study, as these could influence liver function
and metabolic parameters.
5- Some sentences in the manuscript are long and complex, which may hinder clarity. For
instance, the sentence “Notably, some parameters that changed in the AT group no longer
showed significant differences in the AT + RT group, possibly due to the reduced duration of
aerobic activity in the combined exercise regimen…” could be simplified. Please review the text
and break up complex sentences to improve readability.
6- While the study finds that aerobic exercise increases specific bile acid levels (e.g., UDCA,
TUDCA, TCA), further discussion on the roles of these bile acids in liver function would
enhance the manuscript. For example, why does UDCA specifically benefit hepatocytes? What
is the role of TUDCA, TCA, and other conjugated bile acids in improving liver health, and how
does aerobic exercise influence these pathways?
7- While the study provides valuable insights into exercise regimens for young individuals with
NAFLD, it primarily focuses on a specific demographic (young adults). Please address how
these findings might be generalized to other populations, such as older adults or those with
more severe NAFLD. Additionally, consider the limitations of using a short-term (8-week)
intervention period and discuss the need for longer follow-up studies to assess the sustainability
of these benefits.
8- The study provides exercise protocols for both aerobic and resistance training but lacks
detailed information on how intensity and duration were tailored for each participant. For
example, while the aerobic exercise intensity was set to 50%-70% of maximum heart rate,
the intensity for resistance training is not clearly defined. Please provide more details on how
exercise intensity was adjusted for individual participants in both modalities and clarify how it
was monitored throughout the study.
9- Please reference the following articles in the text:
#  High-intensity Interval Training Improves Lipocalin-2 and Omentin-1 Levels in Men with
Obesity
# Differential Effects of Exercise Programs on Neuregulin 4, Body Composition and
Cardiometabolic Risk Factors in Men With Obesity
# Intensity Dependent Effects of Interval Resistance Training on Myokines and Cardiovascular
Risk Factors in Males With Obesity
# Intense circuit resistance training along with Zataria multiflora supplementation reduced
plasma retinol binding protein-4 and tumor necrosis factor-alpha in postmenopausal females
# Effects of Exercise Training on Bone Health Parameters in Individuals With Obesity: A
Systematic Review and Meta-Analysis
Please review this paper.
user
Title: Comparative Effects of Aerobic and Resistance Exercise on Bile Acid Profiles and Liver
Function in Patients with Non-Alcoholic Fatty Liver Disease
Version: 2 Date: 08 Feb 2025
Reviewer:  Ayoub Saeidi
Reviewer's report:
1- In the results section, it is mentioned that there are significant reductions in body shape
parameters (weight, BMI, PBF, WHR) after exercise. However, please provide more statistical
details such as p-values, effect sizes, and confidence intervals for these findings. This will add
rigor to your claims and allow readers to assess the strength of the effects more clearly.
2- While the paper suggests that aerobic exercise improves liver function through bile acid
metabolism, particularly through UDCA, a deeper discussion on the underlying molecular
mechanisms would strengthen the scientific depth of the manuscript. Specifically, please explain
how UDCA and other bile acids impact liver cells on a cellular and molecular level.
3- The combined exercise (aerobic + resistance) group did not show the expected benefits
compared to the aerobic group. It would be valuable to discuss why this combination did not
yield superior results. Could the reduced duration of aerobic exercise in this group have caused
suboptimal results? Are there any physiological mechanisms that may explain why combining
the two types of exercise negates the benefits observed with aerobic exercise alone?
4- It is not clear how adherence to the exercise protocols was monitored. Please clarify whether
any measures were taken to ensure that participants adhered to their assigned exercise regimens.
Additionally, it would be helpful to address whether other confounding factors (e.g., diet, sleep,
stress) were controlled for or monitored during the study, as these could influence liver function
and metabolic parameters.
5- Some sentences in the manuscript are long and complex, which may hinder clarity. For
instance, the sentence “Notably, some parameters that changed in the AT group no longer
showed significant differences in the AT + RT group, possibly due to the reduced duration of
aerobic activity in the combined exercise regimen…” could be simplified. Please review the text
and break up complex sentences to improve readability.
6- While the study finds that aerobic exercise increases specific bile acid levels (e.g., UDCA,
TUDCA, TCA), further discussion on the roles of these bile acids in liver function would
enhance the manuscript. For example, why does UDCA specifically benefit hepatocytes? What
is the role of TUDCA, TCA, and other conjugated bile acids in improving liver health, and how
does aerobic exercise influence these pathways?
7- While the study provides valuable insights into exercise regimens for young individuals with
NAFLD, it primarily focuses on a specific demographic (young adults). Please address how
these findings might be generalized to other populations, such as older adults or those with
more severe NAFLD. Additionally, consider the limitations of using a short-term (8-week)
intervention period and discuss the need for longer follow-up studies to assess the sustainability
of these benefits.
8- The study provides exercise protocols for both aerobic and resistance training but lacks
detailed information on how intensity and duration were tailored for each participant. For
example, while the aerobic exercise intensity was set to 50%-70% of maximum heart rate,
the intensity for resistance training is not clearly defined. Please provide more details on how
exercise intensity was adjusted for individual participants in both modalities and clarify how it
was monitored throughout the study.
9- Please reference the following articles in the text:
#  High-intensity Interval Training Improves Lipocalin-2 and Omentin-1 Levels in Men with
Obesity
# Differential Effects of Exercise Programs on Neuregulin 4, Body Composition and
Cardiometabolic Risk Factors in Men With Obesity
# Intensity Dependent Effects of Interval Resistance Training on Myokines and Cardiovascular
Risk Factors in Males With Obesity
# Intense circuit resistance training along with Zataria multiflora supplementation reduced
plasma retinol binding protein-4 and tumor necrosis factor-alpha in postmenopausal females
# Effects of Exercise Training on Bone Health Parameters in Individuals With Obesity: A
Systematic Review and Meta-Analysis
assistant