-->PONE-D-25-57507-->-->Postprandial Response of Leptin and Adiponectin to Standardized High-Carbohydrate and High-Fat Meals in Adults.-->-->PLOS One

Dear Dr. Soto-Mota,-->--> -->-->Thank you for submitting your manuscript to PLOS ONE. Four external referees have evaluated it, and the consensus is that it is of interest to the journal; however, there are several issues that merit a major revision. Additionally, I have comments the authors should consider to increase the strength of their conclusions.-->--> -->-->Please submit your revised manuscript by Feb 01 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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Additional Editor Comments:

Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

• Please include a STROBE checklist that best adheres to the study design the authors used.
• The phrase “The institutional ethics committee approved the study.” is redundant, considering that the authors previously stated: “The institutional Ethics in Human Research Committee assessed and approved the protocol (reference number 3722).”
• A potential limitation of the study would be the exclusion of individuals living with diabetes, as this population also tends to have differential secretion of leptin and adiponectin, particularly in the elderly population (PMID: 33411633). This could prompt collider bias given the combined prevalence of diabetes and obesity in the Mexican population.
• Leptin seems to have a skewed distribution (given the high SD presented in Table 1). In this regard, did the residuals of the mixed-effects linear regression model fulfill a normal distribution?
• Consider including the 95% confidence intervals of the coefficients reported in Table 2 and Table 3. These could be obtained using the Wald approximation or a semiparametric bootstrap. The lme4 R package further expands these approximations: https://cran.r-project.org/web/packages/lme4/vignettes/lmer.pdf
• Additionally, please specify the fixed effects (time, sex, BMI, meal type) and random effects (individual) used in the models.

Minor comments

• In Table 2, please consider changing the labels to “Men” instead of only “Sex” and “Low-carbohydrate meal” instead of “Meal type.”
• In figures, please be consistent with the labels “Men” and “Women.”
• Table 4 was not appended in the document.
• I believe there is a typo in lines 200 and 240.

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1. Is the manuscript technically sound, and do the data support the conclusions?

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Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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-->2. Has the statistical analysis been performed appropriately and rigorously? -->

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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-->5. Review Comments to the Author

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Reviewer #1: Manuscript Title: Postprandial Response of Leptin and Adiponectin to Standardized High-Carbohydrate and High-Fat Meals in Adults.

Manuscript ID: PONE-D-25-57507

Overall Recommendation: Major Revision

Overall Evaluation:

This study employed a crossover design to investigate the dynamic changes of leptin and adiponectin following standardized high-carbohydrate and high-fat meals, considering the influence of obesity status and sex. The research enrolled 79 adults (including obese and non-obese individuals) who underwent two standardized mixed-meal tolerance tests. Through mixed-effects model analysis, the study found that sex, BMI, and meal composition significantly affected the postprandial trajectories of leptin and adiponectin: both adipokines gradually decreased after a high-fat meal, while their concentrations remained relatively stable after a high-carbohydrate meal.

The topic of this study is relevant, addresses a knowledge gap regarding postprandial adipokine dynamics, and has potential implications for metabolic health. The use of mixed-effects models to capture dynamic responses is a major strength. All main tables, supplementary tables, and Figure 1 are now provided and accessible, greatly facilitating the review process. Figure 1 clearly illustrates the leptin and adiponectin dynamics in different sex and BMI groups after different meals, providing intuitive support for understanding the research results.

However, despite the completeness of all materials, the manuscript still presents several critical issues that must be addressed to meet PLOS One's publication standards, particularly concerning the rigor of methodological descriptions, the integration and interpretation of different statistical analysis results, and the depth of the discussion.

Major Comments:

Data Presentation and Interpretation Issues:

Confusing Citations of Main and Supplementary Tables: The text repeatedly misquotes Main Tables 2 and 4 (which are the primary tables presenting mixed-effects model results) when discussing pointwise comparisons of postprandial leptin and adiponectin. The detailed data for these pointwise comparisons should be presented in Supplementary Tables 2, 3, 4, and 5. For example, lines 174-175: "When comparing meal types, no significant differences in leptin concentrations were observed at any postprandial time point between the high-carbohydrate and high-fat meals (Table 2)." should be corrected to cite Supplementary Table 2. Please carefully check and correct all table citations in the text to ensure the purpose and citation logic of main and supplementary tables are clear.

Detailed Explanation of Mixed-Effects Models (Tables 2 and 3): This remains a core issue, especially given that mixed models are a primary strength of this study. The meaning of their coefficients must be precisely elucidated in the main text:

β-value for "Sex": Please clarify whether it represents an average concentration difference (with females as reference) or a difference in time trends. Based on Table 1 and the negative β-value, this appears to represent an average level difference for males compared to females, which should be explicitly stated in the text.

β-value for "Meal Type" (Leptin: 5.93, Adiponectin: -5.0): Please clearly explain its meaning. Does it represent the average concentration difference for the high-carbohydrate meal relative to the high-fat meal (reference level), or a difference in their overall postprandial trajectories? Given that supplementary tables show no significant pointwise differences, but the mixed model indicates meal type as a significant predictor, this distinction is crucial and requires clear clarification.

Interpretation of "BMI : Meal Type" Interaction Term: For leptin, this interaction term is significant (β = -0.23, p = 0.005), which supports the conclusion that "obese participants exhibited a significantly greater postprandial decline after the high-fat meal." Please elaborate on the biological significance of this interaction effect in the results and discussion, specifically, how the difference in leptin response between the two meal types changes for every one-unit increase in BMI. For adiponectin, this interaction term is not significant, indicating no differential effect of BMI on different meal types, which should also be stated in the text.

Detailed Interpretation of Figure 1: Figure 1 clearly presents the results, but the description and interpretation of Figure 1 in the main text still need strengthening. Please elaborate on the key trends and differences presented in each panel of Figure 1 in the results section, and connect them with the findings from the mixed-effects models (especially interactions). For example, how can the trend that "obese participants exhibited a significantly greater postprandial decline after the high-fat meal" be observed from Figure 1?

Methodological Details:

Inconsistent Description of Study Design: Line 101 of the manuscript still describes it as "This cross-sectional study…", which contradicts the actual "crossover design with repeated measures." Please ensure the study design type is corrected to an accurate description and maintained consistently throughout the manuscript.

Washout Period and Meal Order: This information is still missing. A crossover study design requires an adequate washout period to prevent carryover effects between interventions. Please clearly state the interval between the two MMTTs (washout period) in the methods and justify its adequacy. Additionally, please state whether the order of meal administration was randomized and whether any sequence or period effects were assessed.

Detailed Information on Standardized Dinner: The methods section mentions that "all participants consumed a standardized dinner the evening before each test day." While Supplementary Table 1 provides details of the test meals, the composition of the standardized dinner (macronutrients, calories, specific foods) is equally important for controlling the metabolic state before testing. Please provide these details in the methods or supplementary materials.

Further Clarification of Statistical Analysis:

Clear Distinction Between Wilcoxon and Mixed Models: The manuscript needs to clarify the respective roles of the Wilcoxon pointwise comparisons (Supplementary Tables 2-5) and the linear mixed-effects models (Main Tables 2-3). Wilcoxon tests show differences at specific time points, while mixed models capture overall longitudinal trajectories and interactions. The discussion must clearly reconcile the results of these two analytical approaches, explaining why single time points might not show significant differences, while the overall trajectory is significantly influenced by predictors.

Random Slopes for Time: The current model only includes "random intercepts for participants." Please consider whether "random slopes for time" should be included to account for individual differences in postprandial trends. If not included, please provide a clear justification.

Utilization of R² Values: The marginal R² and conditional R² values of the model have been reported, indicating good explanatory power. Please utilize these R² values more deeply in the discussion to elaborate on the extent to which the selected predictors (sex, BMI, meal composition) explain the variance in leptin and adiponectin levels.

Elaboration of Results and Discussion:

Integration and Logical Coherence of Core Findings: There is a contradiction between the conclusions in the abstract and results section regarding "postprandial leptin and adiponectin gradually decreased after a high-fat meal and remained stable after a high-carbohydrate meal" and "meal composition is a significant predictor," versus the statement in the main text (lines 174-175) that "When comparing meal types, no significant differences were observed at any postprandial time point." The authors must clearly explain this apparent contradiction in the results and discussion. For instance, emphasize that the mixed model captures trends over time or overall effects, while pointwise comparisons may not show significant instantaneous differences due to smaller effect sizes or insufficient statistical power.

Deepening Mechanistic Insights and Expanding References: The discussion section lacks in-depth exploration of potential mechanisms for the observed phenomena (especially the decrease in leptin and adiponectin after a high-fat meal). Please expand this section, incorporating existing literature to discuss possible physiological mechanisms, such as the effects of different macronutrients on insulin, glucose, gut hormones (e.g., CCK, GLP-1), as well as fatty acid types, inflammatory responses, etc. The current number of 13 references is relatively small; it is recommended to supplement with more comprehensive and relevant literature to support the depth of the background and discussion.

Clinical Significance and "Leptin Resistance": The discussion states that "a reduction in leptin, particularly in obese individuals, may impair satiety signals and contribute to excessive energy intake." Please further link this finding to the concept of "leptin resistance," explaining how these postprandial dynamics offer new perspectives for understanding energy imbalance in obesity.

Language and Formatting:

Language Correction: In the abstract, "Contrastingly, stable and did not change significantly after the high-carbohydrate meal" is still missing a subject (e.g., "their concentrations remained stable"). Please carefully check the entire manuscript to ensure fluent language, accurate expression, and correct all grammatical and spelling errors (e.g., "produces" in line 342 "All plots were produces using ggplot2." should be "produced").

Acronym Handling: Ensure all acronyms are defined upon their first appearance. "LCHF" in the list of acronyms is not directly relevant to the meal descriptions in this study; if not further discussed in the main text, it is suggested to remove it.

Table Units and Legends: Please carefully check the units for adiponectin in Supplementary Tables 4 and 5, currently displayed as "(mean ± SD, ng/mL)," which is likely a typo and should be µg/mL. Ensure all tables and figure legends are clear, self-consistent, and contain complete information.

Minor Comments:

Ethics Approval and Data Collection Dates: Lines 106-107 "Recruitment started on July 1st, 2022 and finished on July 31st, 2025" suggest the study is still ongoing. Please confirm whether data collection was completed at the time of manuscript submission. If so, please update the end date to reflect its completed status.

Reference Dates and Format: Dates such as "cited 2025 Sep 21" or "cited 2025 May 15" in the references are still future dates and should be corrected to actual citation or retrieval dates. PLOS One encourages the use of DOIs or PMCID. Please check the reference format to ensure full adherence to PLOS One's guidelines.

Lean Mass Data in Table 1: Table 1 shows that average lean mass for females (49.02 ± 9.86 kg) is higher than for males (43.11 ± 9.83 kg, p=0.011), which contradicts general knowledge for the adult population. Please re-verify these data. If the data are accurate, please provide a reasonable explanation in the discussion (e.g., specific characteristics of the study population, age distribution, body composition measurement methods) or highlight it as a unique finding of this study.

Data and Code Availability: The manuscript submission system indicates data availability as "No - some restrictions will apply," with the explanation that data belong to a biobank and are only accessible to qualified researchers. This is an acceptable exception; please ensure this data availability statement is explicitly included in the methods section or supplementary information of the main manuscript, along with contact information or a process for obtaining the data.

Reporting Guidelines: It is recommended that the authors refer to relevant reporting guidelines, such as STROBE (for observational studies) or STROBE-nut (for nutritional studies), when preparing the revised manuscript to ensure comprehensive and transparent reporting of the research.

Conclusion:

Now, with the complete manuscript content (including Figure 1 and all tables), a comprehensive evaluation is possible. The topic explored in this study is interesting, and valuable findings have been obtained through the use of mixed-effects models. However, to meet PLOS One's rigorous publication standards, particularly regarding the precision of methodological descriptions, the clear integration and in-depth interpretation of different statistical analysis results, and the depth of discussion on potential mechanisms, comprehensive revisions are still required. Please address all the comments above upon resubmission. If these issues can be adequately resolved, I believe this manuscript will make a valuable contribution to the field.

Reviewer #2: This article offers a novel perspective. Despite the relatively small sample size, it has preliminarily uncovered the phenomenon that leptin and adiponectin levels tend to decrease following a high - fat meal. Nevertheless, the study did not conduct an in - depth exploration of the underlying mechanisms. For instance, it remains unclear whether changes in key metabolic signals, such as postprandial insulin, free fatty acids, inflammatory factors, or gastrointestinal hormones, are involved in regulating this response. It is recommended that in the discussion section, possible pathways should be further hypothesized in conjunction with existing literature. Specifically, does high - fat intake result in a reduction in circulating levels by inhibiting leptin secretion or accelerating its clearance? Does postprandial lipemia impact the stability or detection accuracy of adiponectin? Supplementing the relevant experiments to further elucidate the aforementioned potential mechanisms would substantially strengthen the integrity and persuasiveness of the study. These mechanistic considerations will substantially enhance the scientific rigor and theoretical value of the article.

Reviewer #3: Summary: Del Razo-Olvera et al. measured leptin and adiponectin levels following two meals, one high-fat and one high-carbohydrate. They report differences between individuals based on sex, BMI and meal composition.

Overall comments: The manuscript was well written and easy to follow. The introduction and discussion sections included pertinent information, and the study design was thorough. There were only a few comments to improve reader comprehension as outlined below:

1. It would be helpful for the authors to add bar graphs to demonstrate postprandial declines in both leptin and adiponectin between sexes and obese states to more clearly represent differences. These would be in relation to figure 1 and allow for more direct comparisons visually between the different groups.

2. Table 4 is referenced in line 180 but not included in the data.

Reviewer #4: This study by Del Razo-Olvera and co-workers addresses the postprandial responses of two of the most paradigmatic hormones produced by adipose tissue (adipokines), central in the control of metabolic homeostasis (adiponectin) and our relationship with food (leptin), driving together, when defective, the development of lifestyle diseases. The question that they arise is, then, very important, and the study they developed, thus, pretty pertinent. However, it is not true that there is a lack of information regarding the postprandial fluctuations of these two well-known and extensively studied adipokines, or that their concentrations are unaffected by food intake. There is room for improvement in this regard, and quite a lot of very compelling studies dealing with the topic being neglected. The authors need to state crystal clear what’s supposed to be new and what’s confirmatory in their study, and leverage their results with the data of others researchers digging in the topic. Below, there are some other suggestions that the authors of this study can, hopefully, find useful, in order to boost their research results:

Additional points that might improve after revision:

1) Some typos and mistakes have been identified along the manuscript. Please, be careful we word usage.

2) Some references are missing/not very well placed/explained along the text. The authors neglect some key literature on the topic. Please, revise.

3) The plots provided (Fig.1c-d) are okay, but they do not really show the changes the authors claim in the text, apparently provided in supplementary tables. To better contextualising the information provided in text and overall picture, please include any relevant data as main article figures.

4) Some additional markers following the lead of leptin and adiponectin in response to these two dietary inputs may help in boosting the relevance and clinical interest of this study. I am thinking about post-prandial measures of glucose, insulin and ghrelin during the time-course, see to what extent they level adiponectin and leptin fluctuations.

5) Some authors have related the adiponectin-leptin ratio to meta-inflammation (e.g., PMID: 30813240, PMID: 34333093). Do the current results show anything in that line of though?

6) “These results highlight the relevance of dynamic postprandial phenotypes as early markers of metabolic dysfunction.”: Not sure what that means.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: Yes:Francisco J Ortega

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-->PONE-D-25-57507R1-->-->Postprandial Response of Leptin and Adiponectin to Standardized High-Carbohydrate and High-Fat Meals in Adults.-->-->PLOS One

Dear Dr. Soto-Mota,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration and review of the reports from three external referees, we believe the manuscript has potential for publication; however, several issues must still be addressed before we can proceed. We therefore invite you to submit a revised version that responds to the reviewers’ comments and any associated editorial recommendations.

Please submit your revised manuscript by Apr 10 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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-->If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Neftali Eduardo Antonio-Villa, MD PhD

Academic Editor

PLOS One

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

I commend the authors for the extensive work undertaken to address the comments raised by all referees. Please also attend to the remaining points outlined in Reviewer 1’s final considerations.

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1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.-->

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: (No Response)

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The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. -->

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: Partly

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-->3. Has the statistical analysis been performed appropriately and rigorously? -->

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.-->

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: No

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Reviewer #3: Yes

Reviewer #4: Yes

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-->6. Review Comments to the Author

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Reviewer #1: Manuscript ID: PONE-D-25-57507R1

Title: Postprandial Response of Leptin and Adiponectin to Standardized High-Carbohydrate and High-Fat Meals in Adults

General assessment

This manuscript investigates the postprandial dynamics of leptin and adiponectin following two standardized mixed meals with different macronutrient compositions in adults with and without obesity. The topic is clinically relevant and fits well within the scope of PLOS ONE, as it addresses an understudied aspect of adipokine physiology under controlled postprandial conditions.

Overall, the study is methodologically sound, the analyses are appropriate, and the conclusions are generally supported by the data. The revised manuscript is clearly written and substantially improved in clarity and structure compared to the original submission. Importantly, the authors do not overstate novelty and frame their conclusions conservatively, which is appropriate for this journal.

Based on PLOS ONE publication criteria, I believe the manuscript is suitable for publication pending minor to moderate revisions, primarily aimed at clarifying methodology, statistical interpretation, and data availability.

Major comments

1.Study design and crossover clarification

The manuscript states that participants completed two standardized mixed-meal tolerance tests with different macronutrient compositions. However, it is not fully clear whether the study followed a randomized crossover design or whether the order of meal administration was fixed.

Please clarify:

a Whether meal order was randomized or counterbalanced.

b The washout period between test days.

c:Whether potential order or carryover effects were assessed or controlled for.

Clarification is important because postprandial hormonal responses may be influenced by prior dietary exposure.

2.Interpretation of meal composition effects

While the mixed-effects models identify meal composition as a significant predictor of leptin trajectories, pointwise comparisons between meals at individual time points were largely non-significant.

The Discussion should more clearly distinguish between:

a:Statistical significance in trajectory modeling versus

b:Lack of differences at discrete postprandial time points.

At present, the manuscript occasionally implies stronger meal effects than are directly supported by the pairwise comparisons. A more nuanced interpretation would improve scientific rigor and transparency.

3.Adiponectin findings and model interpretation

For adiponectin, the mixed-effects model indicates that meal composition and BMI-by-meal interactions were not significant predictors, yet the Discussion suggests a modest decline after the high-fat meal.

Please clarify whether this decline reflects:

a :A statistically supported trajectory effect, or

b:A descriptive trend without formal statistical support.

If the latter, the language should be softened to avoid overinterpretation.

4.Data availability statement

The Data Availability section indicates that data are part of Mexico’s BIOMEM biobank and are available upon meeting criteria for access.

Please specify:

a:Whether aggregated or de-identified data underlying the figures and tables (e.g., summary statistics) can be made publicly available.

b:The process and contact information for requesting access.

This clarification is necessary to ensure compliance with PLOS ONE’s data availability requirements.

Minor comments

Statistical reporting

Please specify whether residual diagnostics were examined for the linear mixed-effects models.

Clarify whether time was modeled as a continuous or categorical variable.

Terminology

In several places, “stable” is used without an explicit statistical reference. Consider replacing with “did not change significantly” for precision.

Figures

Figures are clear and informative. However, the color gradient representing BMI may be difficult to interpret for readers with color vision deficiencies. Consider whether an alternative or simplified representation is feasible.

Typographical and stylistic issues

Minor grammatical inconsistencies remain (e.g., spacing, punctuation around units). A final careful proofreading is recommended.

Ethical considerations

The study includes appropriate ethical approval and informed consent statements. No ethical concerns were identified.

Reviewer #3: No additional comments. The authors have addressed all relevant comments from reviewers and the editor.

Reviewer #4: The manuscript has improved as much as it could without further experimentation. This reviewer has no further comments.

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Reviewer #1: No

Reviewer #3: No

Reviewer #4: No

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-->PONE-D-25-57507R2-->-->Postprandial response of leptin and adiponectin to standardized high-carbohydrate and high-fat meals in adults: a cross-sectional study-->-->PLOS One

Dear Dr. Soto-Mota,

Thank you for submitting your manuscript to PLOS ONE. I would like to congratulate the authors for their efforts in addressing the reviewers’ comments. I have some final considerations before submitting my recommendation to accept this manuscript. Therefore, I would like invite you to submit a revised version of the manuscript that addresses the points raised during the review process.-->-->

Please submit your revised manuscript by Jun 11 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Neftali Eduardo Antonio-Villa, MD PhD

Academic Editor

PLOS One

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments :

•    The manuscript title describes the study as “cross-sectional,” whereas the cover letter refers to it as a “crossover study.” Please harmonize this accordingly.

•    Please carefully revise Tables 2 and 3 before publication. The reference level for meal type appears inconsistent between the Results text and the table footnotes. The Results state that women and the high-carbohydrate meal were used as reference categories, whereas the table footnotes state that “High in Fats” is the reference level.

•    In the Results, there appear to be some typos in the line: “relatively stablenon-significantly changing adiponectin concentrations.” This should be corrected to “non-significantly changing adiponectin concentrations” or “relatively stable adiponectin concentrations.”

•    The sentence stating that reductions in leptin “could attenuate satiety signaling and contribute to excessive energy intake” should be slightly softened, since satiety, appetite, and subsequent energy intake were not directly measured. I would suggest wording such as: “could potentially influence satiety-related pathways, although this hypothesis requires confirmation in studies directly assessing appetite and energy intake.”

•    Please revise minor typographical issues throughout the text, including “adipoectin,” spacing around references and punctuation, and inconsistent capitalization of “Sex,” “BMI,” and “Meal Type” when they are not table labels.

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

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NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

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Postprandial response of leptin and adiponectin to standardized high-carbohydrate and high-fat meals in adults: a cross-sectional study

PONE-D-25-57507R3

Dear Dr. Soto-Mota,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Neftali Eduardo Antonio-Villa, MD PhD

Academic Editor

PLOS One

Additional Editor Comments (optional):

Congratulations for the exceptional work!

Reviewers' comments: