Ventromedial hypothalamic lesions in rats: gradual elevation of body weight set-point

Bilateral electrolytic (DC) or radiofrequency (RF) lesions of the ventromedial hypothalamic (VMH) area produced two abnormal stages of fattening in adult female rats. Following a negatively-accelerated, curvilinear phase of weight gain which lasted 10 weeks, a linear phase of fattening continued for an additional 30 weeks at a rate approximately double that of operated control rats of the same age. During this second phase of fattening, lesioned rats were food-restricted between the 20th and 26th weeks postlesion. Compared to the rate of weight gain in the linear phase prior to food restriction, the rate over the same weight range following release from food restriction was significantly greater for both DC and RF-lesioned rats. Furthermore, by the 40th postlesion week, the lesioned rats had approached the weight they would have been if not food restricted. These observations suggest that VMH area lesions induce a gradual climbing of the set-point for body weight which occurs independently of actual food intake or body weight, and which either follows or is superimposed on the immediate elevation of the set-point responsible for the initial, curvilinear phase of weight gain. As a model for human idiopathic obesity, the long-term effect of VMH area lesions may be more important than the immediate effect.