As previously demonstrated, OB rats fed a high-fat diet had a higher BM and BF than NOB22–26 rats; similar to the obesity phenotype in humans. Considering literature does not present a defined BMI for rats, and most studies present the issue of BF always related to the respective control groups, our body composition results consolidate our perspective of having a standard of rat body composition. Therefore, we used the same standard of reference for humans ≥ 20% overweight and ≥ 25% obese for men27, being an important reference value for future work with rats. At the end of the experiment, an average of very close to 25% of adult males can be observed, however, our data variability explains a little lower average, and the BM classifies them as obese27, 28, and some animals that had presented BF above 25%, being classified as obese through the BF. Thus, our results are in line with those in the literature, but we would like to observe these alterations over time in more detail, and a gold standard assessment such as the one carried out in the present study, brings this depth.
At week 12, we identified BF close to 20% in OB rats classified as overweight, but the BM was similar to Ambrosi (2011) 27 and Leopoldo (2016) 28 at 15 weeks of obesity induction classified as obese, however, the diet used in the present study had a higher caloric index. Therefore, we believe that week 12 may be the ideal point for inducing obesity. It is important to highlight that the present study presented, at week 24, BM of OB rats greater than that stipulated in literature27, 28.
With regard to FFM, we observed that the greatest increase in the OB group was due to the increase in muscle weight, as we collected the gastrocnemius, soleus, and EDL muscles, both right and left, and the sum of their weight was greater in OB at the end of the experiment, as well as the bone mineral content in the OB group was higher (shown in Figs. 1a and 1b, respectively, in supplementary information). These data corroborate with the literature carried out with humans29 and rats30 since obese people have greater muscle and bone overload. It is worth mentioning that, at the end of the experiment, these animals were middle-aged, and possibly with no signs of sarcopenic obesity appearing, which can affect both the loss of muscle and bone mass31.
Regarding ICP (P2 / P1) ratio of ICP waveform morphology, the difference found between the OB and NOB groups due to the decrease in NOB group is different from Uldall et al. (2017)32 who demonstrated an increase in aquaporin 1 (AQP1), causing an increase in CSF and consequently an increase in ICP. Meanwhile, in their study, they observed values of 7.70 ± 0.42mmHg for OB and 5.86 ± 0.15mmHg in NOB, which despite showing this difference, the values are normal when compared to humans5, similar in the present study that demonstrated ICP shape class I.
Despite the difference between OB and NOB in this study, no animal had a P2 / P1 > 1 ratio being considered potentially pathological or other class, through reference classification, therefore classified normal20. We cannot state the gross ICP value (mmHg) of these animals due to the methodological limitation. There are several causes for the development of intracranial hypertension (ICH)9, it being an idiopathic disease. However, studies have shown that overweight and obesity can lead to ICH8–10, 33, even as the present study demonstrates that obesity can change the ICP waveform morphology (not confirmed by the present study) and that it can be an indicator of the change in ICP values, increasing the possibilities of diseases related both to obesity and to those resulting from increased ICP, as like stroke, blindness, among others.
In addition, when there is an increase in volume inside the cranial box and a decrease in brain elastance and compliance, ICP should increase6, 16, and a small increase in volume to lead to a large increase in ICP. Thus, we infer the lower the P2 / P1 ratio in the NOB group, can be for the better the brain elastance and compliance than OB group, despite animals being sedated during ICP analyses. In the literature, magnetic resonance images demonstrate increased CSF in subdural spaces16 showing brain compliance, with P1 being related to the arterial influx, increasing CBV. However, the subsequent increase in ICP is linked to the CSF outflow, increasing arterial and venous flow interacting, changing the component cranial volume participation. Therefore, good compliance enables accumulation of another cranial volume without higher outflow of CSF, making it difficult to analyze and understand the hemodynamic of this system6 and hampering volume self-regulation. Meanwhile, cerebral compliance was not measured in the present study as well as the mean ICP value in mmHg, and also the value peaks that comprise it (P1; P2; P3). Unfortunately, the system used in this study, as well as other non-invasive ones, does not allow us to know these values and we also did not evaluate the hemodynamic and/or elastance and compliance brain.
Concerning BP, there was no statistical difference between OB and NOB, similar as Shiou et al34 (2018) found, and the absolute BP values (mmHg) of the present study were similar to those found by Shiou et al34 (2018). However, their analysis was invasive, with animals sedated by pentobarbital, and in the present study, BP was performed on the same animals for 24 weeks, which could not be done invasively. Meanwhile, the volume pressure-recording (VPR) sensor used in the present study, has a moderate to high correlation with telemetry and direct blood pressure measurement35. Furthermore, the great variability of our data can also explain this lack of difference in BP. Uldal et al32 (2017) also demonstrated that there is no difference in BP between OB and NOB rats, and indicating that the increase in ICP is not related to the increase in BP and HR, as PA and HR did not change in their studies. However, in the present study, both groups were hypertensive and a difference was found between the HR groups. We found a significant difference in HR between OB and NOB rats, being greater in OB, different from Shiou et al34 (2018) and Uldal et al32 (2017). These data corroborate those of Spereta et al36 (2018) that demonstrated to increase in HR with obese rats, with similar values to the present study. We believe that this difference may be related to increased cardiac work and respiratory rate (not assessed in this study) due to excessive weight. Therefore, may have a link between HR and ICP, despite being sedated during ICP assessment, and this relationship needs to be further studied.