The syndrome of obesity accompanied by dramatically elevated food intake in experimental animals after lesions of the ventromedial hypothalamus (VMH) has occupied a central place in the physiological analysis of feeding and energy balance for several decades. The classic view that the obesity stems from a deficit in the central registration satiety has been largely discredited. Recent years have seen growing interest in peripheral changes, particularly in function of the autonomic nervous system, as a potential basis for the syndrome. Specifically, severing the vagus nerves in the abdomen reverses the hyperphagia and obesity, suggesting a critical role for vagal hyperactivity. Experiments proposed will investigate the basis of this effect of vagotomy. Experiments will examine the role of changes in the vagal-insulin system in VMH obesity in rats. Plasma insulin changes will be determined in response to sham feeding in VMH rats with transections of various branches of the abdominal vagus and related to observed effects of the latter surgery on food intake. One experiment will examine the effectiveness of insulin replacement for restoring hypothalamic hyperphagia. Similar experiments will investigate the role of vagally mediated hyperinsulinemia in the adiposity that develops in VMH rats when food intake is restricted to control amounts. One characteristic of the VMH lesion/vagotomy syndrome is the continued overconsumption of certain diets, such as high fat mash. It is often assumed that this effect reflects continued VMH finickiness after vagotomy. Alternatively, however, it might reflect postingestive actions of the diets. Experiments employing sham feeding and intrasgastric infusion of diets will seek to determine whether the overconsumption results from preingestive or postingestive effects. In light of current interest in metabolic factors in human obesity, study of the VMH syndrome promises to provide clinical insights as to etiology and treatment. At the same time the major changes to insulin release suggest relevance to diabetes.
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