Asperuloside, a natural compound with potent weight-loss properties: a novel therapeutic purinergic signalling approach for the treatment of obesity

Obesity rates are rising dramatically in the developed and developing world and its consequences represent a major public health concern. Current anti-obesity drugs that target metabolic tissues and organs such as the liver, adipocytes and skeletal muscles have failed to deliver significant clinical results. Several studies support the notion that purinergic system has a well-established role in the regulation of energy homeostasis, but there is growing evidence of its implication in the control of food intake. Here, we present the proprieties of asperuloside, an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. Specifically, we investigated some of the mechanisms of action by which the compound induces weight loss in mice consuming a high fat diet. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. We hypothesise that the compound might alter the purinergic signalling via ATP release in response to taste stimulation. As consequence, asperuloside elicits a greater afferent nutrient-sensing signal to the brain which in turn send chemical signals to the hypothalamus for the regulation of food intake. Taken together, our study suggests to evaluate in future studies novel therapeutic purinergic signalling approaches that target the gustatory system as a new and effective anti-obesity strategy.