Hypothalamic hyperinsulinemia and obesity: role of adrenal glucocorticoids

The effects of adrenalectomy on the obesity and hyperinsulinemia induced by ventromedial hypothalamic (VMH) lesions were studied in female rats. Plasma insulin and glucose levels were assayed after a 4-h fast and 17 min after the initiation of a meal (6 ml sweetened milk in 7 min). The development of hypothalamic obesity was prevented by prior adrenalectomy and restored by administration of corticosterone. Adrenalectomy abolished both the basal and postabsorptive hyperinsulinemia observed in sham-adrenalectomized rats with VMH lesions. Corticosterone treatment of adrenalectomized animals enhanced both basal and postabsorptive insulin levels, but adrenalectomized rats with VMH lesions were hyperinsulinemic compared with animals with sham lesions only under the postabsorptive condition. Postabsorptive glucose levels were unaffected by either the lesion or adrenal ablation. The results support our previous conclusion that postabsorptive hyperinsulinemia is of greater importance than is basal hyperinsulinemia in the pathogenesis of hypothalamic obesity. Although the results are consistent with a stimulatory role of corticosterone on food intake mediating the postabsorptive hyperinsulinemia, a primary effect on CNS loci involved with the regulation of insulin secretion is also possible.