This study has examined the effect of obesity and physical activity on the cardiac RAAS in a rat model that is prone to metabolic syndrome – the Zucker rat. The study design is a 2x2 factorial, but not analysed this way, and they have robust methodology for marking the effects of exercise training and/or obesity on their primary endpoint – cardiac RAAS activity. The study is interesting but would benefit from a reevaluation in terms of statistical approach - a statistical advisor should be consulted if the authors fail to understand my below points. Much of the language and tables need correcting for many small errors which just makes one think they have spent a lot less time considering the manuscript than conducting the work that went into it – which is of value. I have a number of other comments as outlined to the authors: For the authors: The statistical treatment of the results is rather weak unfortunately, despite graphs suggesting that you used a factorial design i.e. you have a 2x2 factorial design (excellent) but do no state you analysed the data this way but rather by a weak interpretation using Graphpad – which is excellent for graphs. So i would reinterpret but creating a spreadsheet with a column for bodycomposition (lean/obese) and a column for exercise (yes/no) and analyse your endpoint for the main effects of bodycomp, exercise and interaction bodycomp*exercise. It will far more statistical power as the df are reduced from 3 for all comparison to 1 for bodycomp and 1 for exercise and 1 for the interaction. This will also help your interpretation of the results i.e. Pbodycomp will suggest an effect of being obese per se and so on for the other comparisons. Results – the language here needs tightening up a lot. You refer to diseases a lot, such as cardiovascular disease and metabolic disease. You have only measured risk factors or markers for these rather than the disease process itself as, to my knowledge, rats do not get these disease spontaneously but rather need complex genetic manipulations to get an induced form – such as the Zucker rat. Minor: 1) How can exercise training gradually increase work load to 5% of body weight? I do not understand this statement in the context of what you are describing 2) Is your ‘hypertrophy index’ previously published? It seems a strange index. 3) What are the variabilities for the assays? 4) The tail-cuff procedure is really a challenge to a rat, like air jetting their face, and therefore represents more a stress response than marking chronic or ambulatory ‘hypertension’...Have you previously published your methods for ensuring a standard procedure is used? 5) To my knowledge, cardiologists do not do echocardiography under anaesthesia as the agents used interfere with cardiac function. How do you know your agents did not influence your results and they reflect what is happening in vivo? 6) In results, what is TR. This acronym has not been used before 7) Table 1 – the units need standardising. E.g. 349±10 rather than 10.7. 8) Table 2 - Systolic is spelled incorrectly 9) Table 3 – where are the units?