Objective: To investigate the central regulation of food intake by quantifying neuron activation of the nucleus of the solitary tract (NTS) after injection of cholecystokinin (CCK) or food intake in gastrectomized rats. Summary Background Data: Total gastrectomy is followed by early satiety, low calorie intake, and weight loss in the majority of patients. The etiology of these effects is unknown. Sixty percent to 70% of patients remain underweight after total gastrectomy, the weight loss averaging 25% of preoperative body weight. About two thirds of gastrectomized patients report early satiety, and about 60% do not reach the recommended daily calorie intake. The NTS is a brain stem center involved in the regulation of food intake; thus, the extent and pattern of neuronal activation provide information on the process involved in the initiation of satiation and the regulation of food intake. Methods: The authors investigated neuronal activation in the NTS using c-fos immunohistochemistry following CCK injection or food intake in healthy control rats, sham-operated control rats, age-matched control rats, weight-matched control rats, and vagotomized or gastrectomized rats. Results: Neuronal activation in the NTS after CCK injection was significantly decreased 21 days after total gastrectomy, but increased by up to 51% 3 months and by up to 102% 12 months after surgery compared to age-matched unoperated control rats. Neuronal activation in the NTS in response to feeding was markedly increased up to fivefold in gastrectomized rats. This increase was early in onset and sustained, and occurred despite significantly reduced food intake. Administration of MK329, a CCK-A receptor antagonist, significantly reduced the number of postprandially activated neurons in both gastrectomized and control rats. Conclusions: The early postprandial activation of NTS neurons after total gastrectomy in rats may correspond to early satiety reported by patients, while the sustained activation of NTS neurons after a meal could contribute to a reduced daily calorie intake. These data suggest that a disturbed central regulation of food intake might contribute to early satiety, reduced food intake, and weight loss after total gastrectomy.
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