Chronic stimulation of the cold receptors - TRPM8 on weight gain in obese ob/ob mice: implications for obesity control

Abstract

The recent discovery of temperature sensitive transient receptor (TRP) channels was of extreme importance for a better understanding of the mechanisms of body temperature regulation. Among TRP channels, TRPM8 is characterized as the main channel involved in thermoregulation in responses to cold stimuli, being activated by temperatures below ~ 25°C in vitro and also by the exogenous agonist menthol. Menthol mimics the sensation of cold and activates the 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, however, its efficacy for this purpose has not been fully elucidated. Previous studies from our laboratory showed that chronic topical treatment with menthol promoted hyperthermia as a function of increased metabolism without affecting food intake in Wistar rats, resulting in lower body mass gain in animals treated with the drug, indicating the effectiveness of menthol in preventing weight gain in healthy animals, however, if the treatment is effective to prevent or treat genetics-related obesity is unknown. In this project a genetically modified mouse knockout for the leptin (ob/ob) satiety hormone will be used to verify whether chronic stimulation of peripheral TRPM8 channels alters weight and food intake in these animals. In addition, the influence of chronic stimulation of TRPM8 channels on body temperature will also be evaluated, as well as the locomotor activity of these animals and subsequent analysis of histological changes in white adipose tissue. (AU)