Fetal hypothalamic brain grafts reduce the obesity produced by ventromedial hypothalamic lesions.

Bilateral destruction of the rat ventromedial hypothalamus (VMH) produces a syndrome characterized by hyperphagia and obesity. In the present study we examined whether grafts of fetal hypothalamus could reverse the effects of this lesion. Three groups of adult rats received bilateral electrolytic lesions of the VMH. The first group of animals was then implanted with embryonic day 14-16 hypothalamic tissue by stereotaxic injection into the lesion sites. The second series of animals received comparable-sized grafts from a variety of non-hypothalamic regions of the fetal CNS. The third group experienced similar VMH lesions but did not receive any tissue grafts. After surgery, body weight and food consumption were recorded daily for up to 8 weeks. These measures were compared with similar ones obtained from non-operated rats. Hyperphagia and obesity were consistently observed in all of the lesioned animals not bearing transplants. An initial period of weight gain was also observed in animals receiving hypothalamic grafts, but the duration of the 'dynamic' phase of this syndrome was reduced. Consequently, these graft recipients exhibited significantly less weight gain. This depressed weight gain, however, did not coincide with a statistically significant decrease in hyperphagia. Transplantation of non-hypothalamic tissue also caused an attenuation of the VMH-lesion effect but this was more modest than that induced by homotopic grafts. The results of this experiment show that homotopic transplants can alter the dynamics of weight gain induced by bilateral VMH lesions. However, lesion-induced hyperphagia was not completely reversed in these grafted animals. The fact that other regions can exert a similar effect, though of lesser magnitude, suggests that a more general property of fetal CNS tissue may be involved.