Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Title: Ethanol-soluble compounds underlying the anti-obesity effects 2 of Pometia pinnata (matoa) peel powder in high-fat diet-fed 3 rats: Identification of pancreatic lipase inhibitors

Manuscript ID: nutrients-4128979

 

Comments:

The manuscript infers that fat absorption may be suppressed based solely on pancreatic lipase inhibition assays and an in vitro digestion model. While these findings provide valuable insight, direct measurements-such as fat absorption rate or fecal lipid excretion-are necessary to substantiate the proposed mechanism and strengthen the overall conclusion.

 

The current animal study employs only a single dose (3% MPP or residues) and a relatively short 4-week intervention. Including multiple doses (e.g., 1%, 3%, 5%) of MPP or a standardized extract and establishing a clear dose–response relationship would substantially enhance the robustness of the findings. Extending the feeding period (e.g., 8-12 weeks) and incorporating glucose tolerance tests and insulin sensitivity assessments would also provide a more comprehensive evaluation of the potential benefits on metabolic syndrome–related parameters.

 

The levels of hederagenin saponins and protocatechuic acid in MPP are presently estimated only roughly. Implementing HPLC/LC-MS-based qualitative and quantitative analyses is recommended to accurately determine their concentrations, as well as potential batch-to-batch variations related to geographic origin or fruit maturity. Such characterization is essential for ensuring reproducibility and developing standardized preparations for future clinical applications.

 

For translational relevance, future studies involving overweight or mildly obese adults in short-term interventions (e.g., 4-8 weeks) are encouraged. Key outcomes should include body fat percentage, waist circumference, serum triglycerides, liver function markers, postprandial lipid responses (OGTT or lipid-loading tests), and potential gastrointestinal side effects associated with partial inhibition of fat absorption.

 

Finally, the animal experiment lacks both a normal-diet control group and a positive-control group. With only HF, 3M, 3WR, and 3AR groups-all under high-fat diet conditions-it is difficult to assess whether MPP can restore lipid parameters toward normal physiological levels or how its effects compare with established treatments such as Orlistat. Incorporating these controls in future studies would greatly improve interpretability and contextual relevance.

Author Response

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Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

1. In assessing the anti-obesity activity of Matoa peel powder(MPP), this study focuses primarily on pancreatic lipase inhibition. The authors should provide a more detailed justification for focusing specifically on this mechanism, as it is crucial to establish the rationale behind the experimental design.
2. The authors conducted animal experiments to investigate the anti-obesity effects of MPP; however, the results show no significant change in the final body weight (BW). Given this lack of weight reduction, it is difficult to support the claim that the powder possesses anti-obesity activity. The authors need to re-evaluate their conclusions or provide a compelling explanation for this discrepancy.
3. Furthermore, the data presented in Table 3 do not provide any evidence to support the claimed anti-obesity effects.
4. Even if the pancreatic lipase inhibition is significant, it is difficult to conclude that the extract possesses a definitive anti-obesity effect based on the provided data.

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript „Ethanol-soluble compounds underlying the anti-obesity effects of Pometia pinnata (matoa) peel powder in high-fat diet-fed rats: Identification of pancreatic lipase inhibitors” describes a study aimed to evaluate the effect of compounds derived from matoa on the anti-obesity effects.

Can you explain me the point of applying ethanol extracts of plant material in animal model? The product would not be later consumed in ethanol form. And the negative effect of ethanol itself is very profound in human health.

Line 29-30: this sentence is contradictory. It suggest that the water extract was more efficient but the compounds remained in ethanol? It makes no sense.

Line 82-84: polyphenols and saponins cannot be compared with orlistat. Natural compounds present in food in very low quantities cannot be compared with a pharmacological agent. Of course highly concentrated substance will have more side effects that eating an apple.

Line 90-91: again, I don’t understand why the ethanol extract was prioritized if it didn’t work?

The order of the study design should also be reversed. To conduct the in vivo study with scarifying animals, the screening should be performed in vitro, not the opposite.

The authors wrote in the introduction that the only research gap is the lack of knowledge on the compounds present in this plant and then instead on performing wide metabolomic characterization, the animal study was designed. In my opinion, it does not support the research gap.

The authors wrote that the statistical tools used were as follows: MS Excel, online calculator (for Levele’s test). However, later on the ANOVA test with post-hoc analysis was performed. They cannot be performed in Excel. What software was used?

The observed increased results of liver parameters are associated with alcohol consumption and not necessarily have anything in common with applied intervention.

In Figure 3, it is not specified where part A and B is.

Author Response

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Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript (nutrients-4128979) presents a well-designed and scientifically sound study that addresses an important and timely research question. The objectives are clearly stated, the methodology is appropriate and sufficiently rigorous, and the statistical analyses are properly conducted and well described. The results are presented in a clear and logical manner, and the discussion appropriately interprets the findings within the context of existing literature. The manuscript is well written, organized, and meets the standards expected for publication in this journal.

Author Response

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Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript is well revised.

Author Response

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Reviewer 3 Report

Comments and Suggestions for Authors

I would like to thank authors for clarification. Now the manuscript makes more sence. Still I would suggest removing "ethanol" fro the title, which is long enough and start it with "Compounds contributingo to ....".

Otherwise, all is clear for me now and I have no additional comments.

Author Response

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Author Response File: Author Response.pdf