Effect of vagotomy on hyperinsulinemia in obese rats with hypothalamic lesions.

Abstract

SynopsisWith the purpose of investigating the pathogenesis of obesity and hyperinsulinemia in rats with hypothalamic lesions (HTL), HTL were made in vagotomized rats, and the development of obesity was serially followed In order to elucidate the cause of obesity, we have studied the pathogenesis of obesity in rats with hypothalamic lesions (HTL) and the following results have been reported previously.1. Rats with HTL have a tendency of hyperphagia from the early stage afer HTL and become markedly obese. 2. Fatty acid composition in the adipose tissue shows a decrease of the linoleic: palmitic ratio, and it is mimicked by the administration of insulin to normal rats (Kuwata, 1970). 3. Plasma immunoreactive insulin (IRI) level is markedly elevated, and the pancreatic islets are enlarged after HTL (Chikamori et al., 1973). 4. These alterations observed in the rats with HTL are not influenced by either restriction of food intake (Suzuki, 1970) or hypophysectomy (Hamajo, 1974). 5. Plasma free fatty acid (FFA) and triglyceride levels are elevated in the rats with HTL and the plasma levels of triglyceride and IRI are correlated with the body weight, grade of obesity and the weight of epididymal fat (Chikamori et al., 1973). These results indicate that hyperinsulinemia plays a significant role in the development of obesity in rats with HTL.The hyperinsulinemia in rats with HTL has been attributed to hyperphagia due to HTL (Hales and Kennedy, 1964), increases in insulin antagonists accompanying obesity (Salans et al., 1968), and insulin hypersecretion from the pancreas mediated by the vagal nerve system (Frohman and Bernerdis, 1971), but exact mechanism has been still unknown. Therefore, the present experiments were designed to study the effect of vago-

Consequences of Ventromedial Hypothalamic Lesions upon Insulin and Glucagon Secretion by Subsequently Isolated Perfused Pancreases in the Rat

“…The observation that hypothalamic obesity could not be produced in rats in which B cells had been destroyed by streptozotocin administration and replaced by fetal pancreas transplants devoid of intact innervation (16), supported the concept of a direct neural influence on the B-cell function. Analogous conclusions were drawn on the basis of chronic experiments carried out in VMHlesioned rats with superimposed vagotomy (17)(18)(19) creas (21)(22)(23). Thus, based on the hypothesis of a vagally-mediated hyperinsulinemia in VMH-lesioned animals, one would anticipate changes not only in insulin secretion but in glucagon secretion as well.…”

Hyperinsulinemia: a Cause of Obesity?

“…Lastly, VMH lesions in weanling rats do not induce hyperphagia but still result in HI and accumulation of fat [55]. Multiple groups noted a direct correlation between the change in body weight and the degree of HI following VMH lesion [56, 57]. Pharmacological reduction of insulin alleviates the hyperphagia and weight gain in multiple species [58, 59].…”

The role of hyperinsulinema and the vagus nerve in hypothalamic hyperphagia reexamined

“…Following the initial report of Powley and Opsahl [24] that subdiaphragmatic vagotomy completely abolishes VMH obesity, a number of studies have obtained mixed results. Most experiments report that vagotomy either before or after VMH lesions or knife cuts prevents overeating and obesity [10,18,24,26], but other studies have reported that vagotomy had only a partial or no effect on the hyperphagia syndrome [9,20,36]. Furthermore, in those cases in which vagotomy blocked VMH hyperphagia, some investigators have argued that this is a result of the eating difficulties (dysphagia) produced by the surgery [8,18,20,36], while others contend that vagotomy specifically interferes with the neuroendocrine events responsible for the hyperphagia syndrome [19,24,25].…”