Background. The understanding of the neural pathways involved in thermoregulatory response to cold advanced after the discovery of temperature sensitive TRP channels. Menthol mimics the sensation of cold and activates thermoregulatory mechanisms of cold defense in mammals, promoting hyperthermia and increasing energy expenditure. For this reason, menthol has been suggested as an anti-obesity drug, as it increases metabolism without affecting food intake, resulting in lower body mass gain in lean rodents. The effects of menthol on obese animals however, is unknown. Thus this study aimed at investigating the effects of menthol in both obese ob/ob mice and high-fat diet (HFD) obese rats.

Metodology. Menthol was dissolved in propyleneglycol at a concentration of 5% (w/v). HFD-induced obesity was obtaining by feeding Wistar rats with high fat chow (Rhoster) for 10 weeks. Both obese (ob/ob or HFD) and lean (C57Bl mice and lean wistar rats) were topically treated with menthol or PPG for 9 consecutive or alternate days. Throughout experiment abdominal temperature, total activity and body mass were monitored. All experimental procedures were approved by the Ethics Committee for the Use of Animals of UFABC (CEUA / UFABC #20/2014). Data were analyzed by two-way ANOVA or t-test.

Results. In lean animals (C57Bl or lean Wistar rats) repeated application of menthol resulted in a decrease in body mass gain, which agree with our previous report in lean Wistar rats (Vizin et al, 2018). Menthol treatment was accompanied by a hyperthermic response in both mice and rats (~1°C increase in body temperature compared to control animals), which most probably accounted for the increased energy expenditure that allowed body mass reduction. In obese HFD rats, mentol treatment resulted in a decrease in ~20g in mean body weight, which corresponds to a 5% reduction in body mass. However, in obese ob/ob mice repeated application of menthol was not sufficient to cause a significant reduction on body mass gain. Interestingly, the hyperthermic response of ob/ob mice to menthol was reduced as compared to C57Bl.

Conclusion. We have confirmed our previous results that short-term treatment with topical menthol results in less body mass gain in lean rodents due to a persistent increase in energy expenditure, with limited compensatory thermoregulatory adaptations and, most unexpectedly, without affecting food intake (Vizin et al, 2018). Here, we tested the effects of topical menthol (5%) treatment on body weight gain and body temperature on both genetic obese ob/ob mice and in high fat diet (HFD)-induced obesity in rats. Although topical menthol was not efficient to reduce body mass in ob/ob mice, it reduced body mass in obese HFD rats. Our data supports the suggestion that menthol is a promising drug not only for obesity prevention but also for obesity treatment.