Hypothalamic obesity. The autonomic hypothesis and the lateral hypothalamus

Several lines of evidence support the hypothesis that derangements in the function of the autonomic nervous system play an important role in the development of hypothalamic obesity. Vagotomy below the diaphragm, reverses the syndrome. In diabetic rats cured of their diabetes with transplants of fetal pancreatic tissue beneath the renal capsule, ventromedial hypothalamic (VMH) lesions do not produce the characteristic rise in food intake nor do they significantly increase serum insulin. These observations indicate that the hyperinsulinaemia following VMH lesions is the result of neural connections rather than from a circulating humoral factor released following VMH injury. The smaller salivary glands, reduced level of glucagon and impaired mobilization of fatty acids during stress in VMH lesioned rats point to reduced activity of the sympathetic nervous system. The impaired mobilization of fat from retroperitoneal depots in VMH lesioned rats during fasting is similar to the effect of sympathetic denervation of the retroperitoneal fat pad. Similarly, unilateral sympathectomy caused an increased weight gain in rats almost as much as unilateral VMH lesions but significantly less than in bilaterally lesioned rats. These studies with fasting and feeding implicate the VMH in the control of the sympathetic nervous system. When atropine and epinephrine were given to VMH lesioned rats, there was a significant depression in basal and glucose-stimulated levels of insulin. Finally when VMH lesions were placed after lateral hypothalamic lesions, the effect of the VMH lesions did not seem to be reduced, suggesting that the two effects are independent. A model dealing with the effects of VMH lesions is presented in an attempt to integrate these findings.