The use of vagotomy to treat obesity is now being studied. The vagus nerve provides efferent nervous signals out from the hunger and satiety centers of the hypothalamus, a region of the brain central to the regulation of food intake and energy expenditure. The circuit begins with an area of the hypothalamus, the arcuate nucleus, that has outputs to the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), the brain's feeding and satiety centers, respectively. Animals with lesioned VMH will gain weight even in the face of severe restrictions imposed on their food intake, because they no longer provide the signaling needed to turn off energy storage and facilitate energy burning. In humans, the VMH is sometimes injured by ongoing treatment for acute lymphoblastic leukemia or surgery or radiation to treat posterior cranial fossa tumors. With the VMH disabled and no longer responding to peripheral energy balance signals, "[e]fferent sympathetic activity drops, resulting in malaise and reduced energy expenditure, and vagal activity increases, resulting in increased insulin secretion and adipogenesis. " "VMH dysfunction promotes excessive caloric intake and decreased caloric expenditure, leading to continuous and unrelenting weight gain. Attempts at caloric restriction or pharmacotherapy with adrenergic or serotonergic agents have previously met with little or only brief success in treating this syndrome. " The vagus nerve is thought to be one key mediator of these effects, as lesions lead to chronic elevations in insulin secretion, promoting energy storage in adipocytes. Vagotomy may have an impact upon ghrelin. In an open-label, prospective study of 30 obese patients (26 women), response has been variable; the intervention has generally been safe, although adverse events have included gastric dumping syndrome (n=3), wound infection (n=2), other (n=5), and diarrhea (n=6).