Effects of vagal and splanchnic section on food intake, weight, serum leptin and hypothalamic neuropeptide Y in rat.

Truncal vagotomy can cause reduced food intake and weight loss in humans and laboratory animals. In order to investigate some of the factors that might contribute to this effect, we studied changes in ingestive behaviour, whole body and organ weights, serum leptin and hypothalamic neuropeptide Y in rats with bilateral vagal section, bilateral splanchnic nerve section and combined vagotomy plus splanchnectomy. Pyloromyotomy was combined with vagotomy to lessen effects of vagotomy on gastric emptying. Animals with vagotomy or vagotomy plus splanchnectomy lost weight and decreased their daily food intake relative to animals with splanchnectomy alone, rats with bilateral sham exposure of one or both nerve, or rats with pyloromyotomy alone. Serum leptin and white fat mass, 4 weeks after vagotomy, were about 20% of the values in the sham-operated animals at this time. No effect for splanchnic nerve section alone was observed. Pyloromyotomy caused no reduction in weight or fat mass, but reduced serum leptin. Following vagotomy with or without splanchnic nerve section, neuropeptide Y was elevated in the arcuate nucleus relative to values for the other four groups. Changes in neuropeptide Y were inversely correlated with levels of serum leptin. It is concluded that the effect of vagotomy could be due to the loss of a feeding signal carried by vagal afferent neurons, or to changed humoral signals, for example, increased production of a satiety hormone. However, it cannot be attributed to signals that reduce feeding (for example, gastric distension) reaching the central nervous system via the splanchnic nerves. The changes were sufficient to cause weight loss even though serum leptin was decreased, a change that would be expected to increase food intake.

Hypothalamic hyperphagia and obesity in rats with jejunoileal bypass.

Jejunoileal bypass or sham surgery was performed in adult female rats followed 35 days later by ventromedial hypothalamic (VMH) knife cut or sham surgery (forming groups Bypass-VMH, Bypass-Sham, Sham-VMH, and Sham-Sham). Bypassed rats receiving VMH cuts (Bypass-VMH group) ate more food and gained more weight than did either Bypass-Sham or Sham-Sham groups. The hyperphagia and obesity of the Bypass-VMH rats was, however, substantially less than that of the sham bypass VMH cut rats (Sham-VMH group). Bypass-VMH rats that had their intestinal tract reconnected increased their food intake and ultimately became as obese as the Sham-VMH rats. Two additional groups received VMH knife cut or sham surgery followed 50 days later by jejunoileal bypass surgery (VMH-Bypass and Sham-Bypass groups). At the time of the bypass the VMH-Bypass group was hyperphagic and obese, but after surgery they underate and lost weight until they eventually stabilized their body weight at a level below that of the Sham-Bypass group. The body weight of the VMH-Bypass group was also 167 g less than that of the Bypass-VMH group. Thus, the order of surgery significantly influences the food intake and body weight level of rats with VMH knife cuts and jejunoileal bypass.

Effects of intestinal bypass surgery on appetite, food intake, and body weight in obese and lean rats.

Jejunoileal bypass surgery or sham surgery was performed in female rats made obese with ventromedial hypothalamic (VMH) knife cuts, and in lean control rats. After bypass surgery, the VMH rats underate and lost weight until they reached the body weight of the control sham rats, and they then maintained their weight at control levels. Bypass surgery in lean rats produced much smaller reductions in food intake and body weight. Both bypass groups initially consumed less of a sucrose solution and milk diet during 1 h/day tests, but their intakes returned to near normal levels during the second postoperative month. Reconnection of the intestinal tract in the VMH-bypass rats led to renewed hyperphagia and return to obese body weights. A second experiment revealed that bypass surgery reduces food intake and body weight in genetically obese (fatty) rats, but this effect is not as pronounced as that displayed by VMH rats. These results confirm recent clinical observations that reduced appetite and caloric intake are the major causes of the weight loss produced by intestinal bypass surgery.