Review History


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Summary

  • The initial submission of this article was received on September 16th, 2024 and was peer-reviewed by 4 reviewers and the Academic Editor.
  • The Academic Editor made their initial decision on November 24th, 2024.
  • The first revision was submitted on February 11th, 2025 and was reviewed by the Academic Editor.
  • The article was Accepted by the Academic Editor on March 16th, 2025.

Version 0.2 (accepted)

· Mar 16, 2025 · Academic Editor

Accept

I have assessed your revisions and judge that they largely address the reviewers initial concerns. I'm happy with the current version and regard it as ready for publication.

[# PeerJ Staff Note - this decision was reviewed and approved by Stefano Menini, a PeerJ Section Editor covering this Section #]

Version 0.1 (original submission)

· Nov 24, 2024 · Academic Editor

Major Revisions

We received thoughtful comments from four referees on your manuscript. I would like you seriously consider each one. In particular, Referee 2 has a detailed set of comments that would, I believe, substantially improve the manuscript.

[# PeerJ Staff Note: It is PeerJ policy that additional references suggested during the peer-review process should *only* be included if the authors are in agreement that they are relevant and useful #]

·

Basic reporting

1. Rewrite the lines 85 to 87, as the sentence is ambiguous.
2. Line 227 and 228 language used is not clear.

Experimental design

1. Please clarify the total number of loci genotyped using Illumina platform, proportion of them filtered and are not in HW equilibrium, quote the reference of using SNP call rate. Why it was taken to be more than 905 but not the 95%. Some information might have been lost.
2. Heterozygotes are considered to be more fit under natural selection theory, whether your results are on the same lines? please describe

Validity of the findings

No comments

·

Basic reporting

I congratulate the authors for their interesting study titled "Association between adenylate cyclase 3 gene polymorphisms and the effects of high-intensity interval training on blood lipid" where the role of the rs2241759 polymorphism in modulating lipid profile changes induced by high-intensity interval training (HIIT) in young Chinese adults was investigated. The research offers valuable insights into the biological factors influencing individual responses to HIIT. However, I believe the manuscript requires major revisions before it can be suitable for publication. Specific comments are provided for each section of the manuscript.



Reporting Bias: The authors did not discuss the sexual dimorphism in the association of the rs2241759 polymorphism and lipid profile response to HIIT. This omission is a significant limitation, given that differences on lipid profile modifications after HIIT were observed under a codominant model for males (AG/GG), but a dominant model was observed for females (AA/AG).

Molecular Mechanisms: The manuscript would benefit from a deeper discussion of the molecular mechanisms through which the rs2241759 polymorphism might affect the activity of adenylyl cyclase 3 and its downstream impact on lipid metabolism. This would help to contextualize the study's findings within the broader literature.

Grammar and Style: Finally, the manuscript requires substantial revision in terms of grammar and writing style to improve clarity and coherence.

I have provided additional specific comments to the authors following the journal's guidelines.

Experimental design

- Experimental design
Was this a single arm longitudinal study?
If so, please specify how many of the recruited individuals completed the exercise intervention. Reasons for abandonment should be also reported to ensure the fulfillment of Ethical Guidelines for Exercise and Sports Sciences studies.
Harriss, D. J., Jones, C., & MacSween, A. (2022). Ethical Standards in Sport and Exercise Science Research: 2022 Update. International journal of sports medicine, 43(13), 1065–1070. https://doi.org/10.1055/a-1957-2356

- Body weight and Height Assessment
There is not a description of the materials and methods used to examine the participants body weight and height. These data just appeared in Table 1

- Inclusion criteria
How were the health status and exercise experience examined?
Did the authors applied a health survey? Did the authors applied a physical activity questionnaire?

-Exercise protocols for evaluating cardiorespiratory fitness (VO2max)
The authors report that %VO2max was used to control the exercise intensity during the HIIT. However, they never described the exercise protocols applied to examine VO2max their participants. These details are crucial for validating the HIIT as there is no way to standardize exercise intensity by only using predictive VO2max (or HRmax) equations.

-Locations and facilities for HIIT
The authors does not specify if the exercise intervention was carried out in the same location. This was a large cohort intervention. Were all of the participants trained simultaneously or was the project divided on distinct experimental phases?. If so, please specify the intervention period.

In case the exercise intervention toke place on different locations, please specify how many trainers/technicians were involved? The authors stated that Beijing Sports University toke charge of the experiment and offered technical guidance but they don't provide the details about such training process. This is important to validate the accuracy of the training interventions.

Were the exercise sessions performed on a treadmill or a track? There is no description of the ergometers or facilities used during the HIIT.

-Description of HIIT
There is no need to describe the workload progression during the HIIT as this is already provided in Table 2. Instead the authors should specify how have they examine the VO2max and HRmax (see my previous comment)

Validity of the findings

- Sexual dimorphism on the association of the rs2241759 polymorphism with the lipid profile response to HIIT

The authors did not discuss the sexual dimorphism in the association of the rs2241759 polymorphism and lipid profile response to HIIT. This omission is a significant limitation given that differences on lipid profile modifications after HIIT were observed under a codominant model for males (AG/GG), but a dominant model was observed for females (AA/AG).

- Linear regression analysis
Please report the details of the linear regression computed to estimate the association of the rs2241759 polymorphism with the lipid profile response to HIIT.
Was the rs2241759 polymorphism a better predictor than age and sex?
How was the interaction between these biological predictors?
Which was the R2 and RMSE of the model?
How were the assumptions of normality and multicollinearity verified?

- Effect sizes
When describing the differences between genotype groups, please provide the effect size

- Molecular Mechanisms related to the rs2241759 polymorphism
The manuscript would benefit from a deeper discussion of the molecular mechanisms through which the rs2241759 polymorphism might affect the activity of adenylyl cyclase 3 and its downstream impact on lipid metabolism. According to the SNP database of the NCBI, this polymorphism is a synonym mutation. Then, how could this affect the activity of the encoded protein? Wouldn't it work regularly?

The variants discussed from the authors to argue the potential impact of the ADCY3 gene on lipid metabolism are intronic variants. These have the potential to alter the nuclear transcription of the gene and therefore the adenylyl cyclase 3 levels. However, the SNP examined in this study may work through a different mechanism (see my previous comment).

Additional comments

-The manuscript would benefit from substantial revision in terms of grammar and writing style.
Some examples were grammar revisions are necessary are provided below:

Line 90— ´´Exercise is an effective method to ameliorate blood lipid status´´

Exercise is an effective method to prevent/treat dyslipidemia

Line 103-106 ´´LDL-C value increased in participants with GA/AA genotype, who with the rs693 single nucleotide polymorphism (SNP) locus of ApoB gene(Tamburus et al. 2018). Explain the association between gene polymorphism and the effects of HIIT on blood lipid´´.

LDL-C values increased in carriers of the rs693 single nucleotide polymorphism (SNP) (Tamburus et al. 2018)

- Efficiency of the HIIT to improve the blood lipids profile
The study of Martin-Smith et al., (2020) does not provide direct evidence of a superior benefit of HIIT over moderate intensity continuous training. Indeed, controversial results about the efficiency of HIIT to improve the lipid profile have been reported in the literature, depending on the examined population.

Wood, G., Murrell, A., Touw, T., & Smart, N. (2019). HIIT is not superior to MICT in altering blood lipids: a systematic review and meta-analysis. BMJ Open Sport — Exercise Medicine, 5. https://doi.org/10.1136/bmjsem-2019-000647.

McCORMICK, C., Mamikunian, G., & Thorp, D. (2023). The Effects of HIIT vs. MICT and Sedentary Controls on Blood Lipid Concentrations in Nondiabetic Overweight and Obese Young Adults: A Meta-analysis.. International journal of exercise science, 16 3, 791-813 .

This should be addressed both in the introduction and the discussion where the authors only provide studies in favor of HIIT, leading to a biased interpretation of the results.

Reviewer 3 ·

Basic reporting

The current study investigated the association between adenylate cyclase 3 gene polymorphisms and the effects of high-intensity interval training on blood lipid. I suggest the authors to revise the article in line with some suggestions.

Experimental design

The method seems well planned.

Validity of the findings

Most of the results are quite interesting and are well discussed.

Additional comments

Title
You can add the RS code to the title.


Abstract

In the text, physical activity is sometimes referred to as “exercise,” sometimes as “sport,” and sometimes as “training.” To ensure flow and maintain consistency, a single term should be used, as each has a different meaning. Please express the sentence fluidly using just one term.

Introduction
The introduction is generally well-written; however, it includes very limited information on genetic research. It would be beneficial to incorporate some genetic studies, especially using recent references.
https://doi.org/10.1113/EP091992



Participants

Detailed information about the participants should be provided, such as age, gender, etc.
Information about ethnic origin can be provided.

Training plan of HIIT

You mentioned that the same exercise load was applied in both the first and second phases. Do you think this is correct?

Secondly, how did you ensure homogeneity or control across different groups at various universities? Do you believe this is an appropriate technique for producing accurate results?


Discussion

It seems that the English is clear, but research articles usually do not use the word “we/our” and regularly use passive verbs.

Line 27-28: There are some non-English words

Most of the results are quite interesting; however, they are not thoroughly discussed.

Line 228, 232: This study further supports our findings. You can explain to the reader why there is such a similarity. What’s your suggestion? Etc.

If there is a difference between men and women, can you explain in detail why?

Annotated reviews are not available for download in order to protect the identity of reviewers who chose to remain anonymous.

·

Basic reporting

Lai et al. investigated the effect of HIIT on improving lipid profile status among college students. The work was conceptualized and executed well. HIIT improved lipid status and mimicked the ADCY3 gene rs2241759 as per the results obtained from this study. However, the discussion section needs improvement. My specific comments are as follows:
Line no: 222; Why was obesity introduced without any reason? Were college students obese?
Line no: 245; The authors discussed how HIIT decreased inflammation and mentioned some markers like TNF-alpha, IL-1, and IL-8. However, I don’t find any inflammatory markers studied in this research. The authors must explain why and how their study results correlated with these markers.
I don’t find any inflammatory markers studied in this study. However, why did they discuss inflammatory markers in relation to HIIT?
Line no 98: A genetically modulated role for 99 ACE in the control of glucose import and oxidation in working skeletal muscle (rewrite it).

Experimental design

Experiments were carried out according to the concept. I do not find any problem with the experimental setup.

Validity of the findings

N/A

Additional comments

N/A

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