The Potential Role of Activating the ATP-Sensitive Potassium Channel in the Treatment of Hyperphagic Obesity

To evaluate the potential role of ATP-sensitive potassium (K(ATP)) channel activation in the treatment of hyperphagic obesity, a PubMed search was conducted focused on the expression of genes encoding the K(ATP) channel, the response to activating the K(ATP) channel in tissues regulating appetite and the establishment and maintenance of obesity, the evaluation of K(ATP) activators in obese hyperphagic animal models, and clinical studies on syndromic obesity. K(ATP) channel activation is mechanistically involved in the regulation of appetite in the arcuate nucleus; the regulation of hyperinsulinemia, glycemic control, appetite and satiety in the dorsal motor nucleus of vagus; insulin secretion by β-cells; and the synthesis and β-oxidation of fatty acids in adipocytes. K(ATP) channel activators have been evaluated in hyperphagic obese animal models and were shown to reduce hyperphagia, induce fat loss and weight loss in older animals, reduce the accumulation of excess body fat in growing animals, reduce circulating and hepatic lipids, and improve glycemic control. Recent experience with a K(ATP) channel activator in Prader–Willi syndrome is consistent with the therapeutic responses observed in animal models. K(ATP) channel activation, given the breadth of impact and animal model and clinical results, is a viable target in hyperphagic obesity.