Nonirritative lesions of VMH: effects on plasma insulin, obesity, and hyperreactivity

Obesity resulting from lesions of the ventromedial hypothalamus (VMH) has often been attributed to ablation-induced disinhibition of insulin release. However, lesion studies have generally employed electrolyzing anodal current with stainless steel electrodes, which results not only in tissue ablation but deposits of metallic ions that can chronically irritate surrounding tissue. The present study compared the effects of irritative and nonirritative VMH lesions on plasma insulin levels and obesity in female rats. Blood samples were obtained after a 4-h fast and 17 min after the initiation of a meal (6 ml of sweetened milk in 7 min) during a period when VMH rats were food restricted to the level of sham-operated animals and again when all animals were fed ad libitum. Irritative lesions (anodal electrolytic with stainless steel electrodes) caused heavy metallic ion deposition at the lesion site, marked obesity, and hyperinsulinemia both during food restriction and ad libitum feeding. Nonirritative lesions (cathodal electrolytic with platinum electrodes) resulted in no metallic ion deposition in seven of nine animals. These seven rats, which displayed 65% of the weight gain of animals with irritative lesions (significantly greater than sham rats), had significantly elevated insulin levels only under the postabsorptive condition during ad libitum feeding. In addition, only the animals with irritative lesions displayed emotional hyperreactivity to capture and handling. It is concluded that obesity produced by anodal electrolytic lesions with stainless steel electrodes is a result of both a destructive component resulting in hyperphagia with secondary hyperinsulinemia and an irritative component (accounting for up to 40% of the weight gain in female rats) resulting in basal hyperinsulinemia independent of hyperphagia.(ABSTRACT TRUNCATED AT 250 WORDS)