## 4 Discussion
It is interesting that no significant differences were observed in the glucose tolerance test, given the significant differences in carbohydrates excreted. However, only one test was given at 10 weeks. It would be worthwhile assessing whether there were significant differences in glucose tolerance at different stages. Given the previous evidence supporting the ability of PRSE to inhibit the uptake of glucose [17] it is also possible that the polyphenols assisted in mitigating the excessive storage of the energy provided to the diet by the glucose tolerance test at week 10. Whilst leptin is a hormone involved in signaling satiety, detection of high leptin levels correlates with high-fat diets and obesity and therefore has become an indicator of the development of leptin resistance [28]. This hypothesis was supported in the present trial by the significantly higher leptin concentration detected in control mice, compared to the 4% PRSE treatment. Other studies on polyphenols in rodent models that reported reduced obesity have also been associated with similar leptin responses [29; 30]. There were no significant differences detected in adiponectin levels in plasma. A similar study that observed weight loss in the presence of lemon polyphenols also found a significant decrease in plasma leptin, without significant differences to adiponectin levels [29]. Surprisingly, in our study the expression of adiponectin mRNA was significantly higher in both treatment groups compared to control, despite no differences observed in the plasma adiponectin hormone levels. Unfortunately, the lemon polyphenol study did not analyse adiponectin mRNA levels to see if the same trend occurred [29]. Whilst it is difficult to be certain why there is a discrepancy between the mRNA levels of adiponectin and the circulating levels of the hormone detected via ELISA, some insights into the physiological effect correlated with an elevated mRNA expression level can be made. Mice with genetically induced overexpression of adiponectin mRNA have been shown to be protected against both the acute and chronic damage caused by exposure to a high-fat diet [31]. It could therefore by hypothesized that upregulation of adiponectin by PRSE treatment may represent an increasing metabolic flexibility that, once activated by PRSE, is better equipped to respond to the challenge of the high-fat diet used in this trial. Alternatively, mRNA does not always correlate with protein adiponectin levels, therefore this discrepancy may be an example of this circumstance [32]. Adiponectin is known to activate PPAR1\(\gamma\), which was also mirrored in this trial by the upregulation of the PPAR1\(\gamma\) mRNA in a dose-dependent manner to the adiponectin mRNA expression [33]. In contrast, other polyphenols such as compounds derived from green tea [34] and acacia [35] that have been observed to have anti-obesity propertieshave been suggested to be acting via the downregulation of PPAR1\(\gamma\). However, other studies have reported weight loss that was attributed to the upregulation of PPAR1\(\gamma\). A study on lemon verbena polyphenols observed anti-obesity effects induced by a PPAR1\(\gamma\) dependent mechanism [36]. It is likely that the anti-obesity effects of PRSE were also mediated by a similar mechanism. The authors [36] also hypothesized that protection of mitochondrial function, AMPK activation and anti-inflammatory effects were crucial components of the action of the anti-obesity effects of the lemon verbena polyphenols. Therefore, future studies into the underlying mechanisms of PRSE would benefit from the inclusion of these parameters to further understand the bioactivity of PRSE. Another study on peach and plum juice showed an increased PPAR1\(\gamma\) expression alongside polyphen-induced weight loss [37]. These authors suggested this activation of PPAR1\(\gamma\) via dietary polyphenols as an aspect of the mechanism of action [37]. However, it is surprising that the increased PPAR1\(\gamma\) observed did not lead to an increased plasma adiponectin level [38].