Pathogenesis in Human Obesity: Function and Disorder of a Mechanism of Satiety

Summary There has been presented an alternative to the hypothesis that an increased drive to eat leads to the hyperphagia of obese persons. Evidence from laboratory animal experiments suggests that satiety may represent not merely the passive extinction of a drive but an active process with an internal dynamics of its own. If this is true, a disorder in this process may give rise to the overeating of some obese persons by the same mechanism which provokes the hyperphagia of the hypothalamically damaged rat. Evidence has been adduced that a "glucostatic" mechanism may play a role in normal satiety. In considering where this mechanism may become disordered in obese persons there seem to be two major possibilities: There may be a breakdown in the mechanism itself, so that an adequate carbohydrate supply is inadequately signaled to the food‐regulatory centers of the hypothalamus. There is evidence that this does not occur. On the other hand, in certain obese women during stress intravenously administered glucose is removed from the peripheral blood at a greatly increased rate. If ingested glucose is as rapidly utilized it could provide a stimulus to the glucostatic mechanism for only a very brief period of time, and thus might fail to interrupt the periods of overeating in more than a transitory manner. Such a functional disorder of the satiety mechanism could thereby lead to hyperphagia and obesity in much the same manner as does destruction of the hypothalamic satiety centers. This work tends to confirm the widely held impression that obesity represents an inappropriate adaptive response, and presents evidence that in some persons this response involves a disturbance in carbohydrate metabolism.