The Impact of Chronic Stress and Eating Concern on Acylated Ghrelin Following Acute Psychological Stress in Healthy Men

Round 1

Reviewer 1 Report

In the present manuscript entitled ” The impact of chronic stress and eating concern on acylated ghrelin following acute psychological stress in healthy men” the authors deal with an interesting issue of impact of chronic and acute stress and their connection with acylated ghrelin in healthy men. The present manuscript even if deals with important concepts suffers of some inconsistencies that require substantial revisions prior to reach publication priority.

Minor but essential revisions

1. Why the study was conducted only on male subjects? It well known that female subjects are more subject to the effect of stress.
2. Why don’t be assessed other hormone stress as well as cortisol, norepinephrine and epinephrine
3. How do the authors explain the differences in the effects of acute stress on ghrelin compared to chronic stress?
4. Why the authors don’t assess the levels of leptin on satiety considering that it has a crucial role?
5. I suggest adding a sub-paragraph describing the effects of stress on hunger with consequent health implications such as diabetes, metabolic syndrome and cancer.
6. I suggest to quote following papers:

• Barbieri A, Bimonte S, Palma G, Luciano A, Rea D, Giudice A, Scognamiglio G, La Mantia E, Franco R, Perdonà S, De Cobelli O, Ferro M, Zappavigna S, Stiuso P, Caraglia M, Arra C. The stress hormone norepinephrine increases migration of prostate cancer cells in vitro and in vivo. Int J Oncol. 2015 Aug;47(2):527-34. doi: 10.3892/ijo.2015.3038. Epub 2015 Jun 8. PMID: 26058426.
• Barbieri A, Palma G, Rosati A, Giudice A, Falco A, Petrillo A, Petrillo M, Bimonte S, Di Benedetto M, Esposito G, Stiuso P, Abbruzzese A, Caraglia M, Arra C. Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth. J Cell Mol Med. 2012 Apr;16(4):920-6. doi: 10.1111/j.1582-4934.2011.01375.x. PMID: 21722303; PMCID: PMC3822860.

Author Response

We would like to thank the reviewer for putting his/her time and effort into improving our manuscript.

Why the study was conducted only on male subjects? It well known that female subjects are more subject to the effect of stress.

Thank you for your comment. We decided to perform the study using only participants of one gender to minimize the variability of the results. The nutritional patterns of females’ are more complex and females' diet choices are stronger influenced by multiple factors (eg. environment, cues, emotions, moods). Considering that we wanted to investigate the impact of stress only we decided that by choosing male participants we reduce the impact of confounding factors.

Why don’t be assessed other hormone stress as well as cortisol, norepinephrine and epinephrine

Indeed, it is a very good idea to assess the levels of stress hormones to confirm the effectiveness of stress induction. However, in our study, we decided to use other means confirming the success of the treatment, including heart rate and PANAS. Therefore, we do not possess data for concentrations of the mentioned hormones.

How do the authors explain the differences in the effects of acute stress on ghrelin compared to chronic stress?

We assume that the subjects with high chronic stress exposure have different stress-response thresholds compared to low chronic stress individuals leading to the differences in acylated ghrelin response. However, it may also indicate altered ghrelin sensitivity and adjustment of the active ghrelin levels to the current threshold of the sensitivity of ghrelin receptors. We included a corresponding comment in the discussion section.

Why the authors don’t assess the levels of leptin on satiety considering that it has a crucial role?

Again, a very relevant suggestion. The study would benefit from much more than just ghrelin levels measurement. Besides stress mediators also leptin is a very relevant factor in this case. We asked the participants to fill the 24h recall and we gave them standardized breakfast to ensure similar levels of satiety as far as we could. However, leptin levels are also influenced by stress and therefore, of interest for the study. However, we focused mainly on ghrelin and we do not possess data for concentrations of leptin. Unfortunately, here our financial situation was a limiting factor for the study.

I suggest adding a sub-paragraph describing the effects of stress on hunger with consequent health implications such as diabetes, metabolic syndrome and cancer.

Thank you for your suggestion. The introduction has been modified accordingly.

I suggest to quote following papers:

• Barbieri A, Bimonte S, Palma G, Luciano A, Rea D, Giudice A, Scognamiglio G, La Mantia E, Franco R, Perdonà S, De Cobelli O, Ferro M, Zappavigna S, Stiuso P, Caraglia M, Arra C. The stress hormone norepinephrine increases migration of prostate cancer cells in vitro and in vivo. Int J Oncol. 2015 Aug;47(2):527-34. doi: 10.3892/ijo.2015.3038. Epub 2015 Jun 8. PMID: 26058426.
• Barbieri A, Palma G, Rosati A, Giudice A, Falco A, Petrillo A, Petrillo M, Bimonte S, Di Benedetto M, Esposito G, Stiuso P, Abbruzzese A, Caraglia M, Arra C. Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth. J Cell Mol Med. 2012 Apr;16(4):920-6. doi: 10.1111/j.1582-4934.2011.01375.x. PMID: 21722303; PMCID: PMC3822860.

Thank you. The suggested articles have been cited in the introduction.

Reviewer 2 Report

The manuscript was well written and presented. Make sure all abbreviations are defined when the first appear eg DEBQ on line 68

Author Response

The manuscript was well written and presented. Make sure all abbreviations are defined when the first appear eg DEBQ on line 68

Thank you for your comment. The mistakes have been corrected.