Serotonin Receptor Blockade Increases Food Intake and Body Weight after Total Gastrectomy in Rats

Zittel, Tilman T.; Glatzle, Jörg; Weimar, Timo; Kless, Steffen; Becker, H. D.; Jehle, E. C.

doi:10.1006/jsre.2002.6463

Cited by 12 publications

(4 citation statements)

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“…Appetite is regulated by the hypothalamus via many hormones. Although it is still controversial, some studies speculate appetite loss after gastrectomy to be associated with increased intestinal hormones such as cholecystokinin [2,25,26] and serotonin [26,27]. The present study suggests that ghrelin may play a central role in regulating appetite by the digestive tract.…”

Section: Discussionmentioning

confidence: 58%

“…In addition, it impairs the immune system [39], making the patient more susceptible to infectious disease and cancer recurrence. Antagonists of intestinal hormones, including cholecystokinin or serotonin, have been reported to increase body weight after gastrectomy in animal experiments [27,40] and their clinical application has been considered. However, the side effects of such non-physiological compounds have not been evaluated.…”

Section: Discussionmentioning

confidence: 99%

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Postoperative Ghrelin Levels and Delayed Recovery from Body Weight Loss after Distal or Total Gastrectomy

Takachi

Doki

Ishikawa

et al. 2006

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Postoperative Ghrelin Levels and Delayed Recovery from Body Weight Loss after Distal or Total Gastrectomy

Takachi

Doki

Ishikawa

et al. 2006

Journal of Surgical Research

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“…Metergoline, at 3 mg/kg that nonselectively blocks 5-HT 1, 2, and 7 receptors (19), was the only antagonist that significantly affected caloric intake on its own, inhibiting it by 24% ( Table 1; Student's t-test P < 0.001). The effect of metergoline on food intake highly depends upon the dose and feeding setup; metergoline reduces food intake when rats have limited access to food (20), but in satiated or gastrectomized rats it may even increase caloric intake (20,21). SIB 3 mg/kg significantly decreased total caloric intake by 46% during the 18-h feeding period in rats (Figure 1; F(10,98) = 13.39, P < 0.0001, post hoc P < 0.001).…”

Section: Articles Intervention and Prevention Results The Effects Of mentioning

confidence: 99%

Inverse Agonism at α2A Adrenoceptors Augments the Hypophagic Effect of Sibutramine in Rats

Janhunen

Zwaal

Fleur

et al. 2011

Obesity

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Because the use of monoamine reuptake inhibitors as weight‐reducing agents is limited by adverse effects, novel antiobesity drugs are needed. We studied acute effects of the noradrenaline (NA) and serotonin (5‐HT) reuptake inhibitor sibutramine (SIB), alone and after pretreatment with α1‐ and α2‐adrenoceptor (AR), and 5‐HT1/2/7, 5‐HT1B and 5‐HT2C receptor antagonists in order to determine which ARs and 5‐HT receptors act downstream of SIB on feeding and locomotion. Acute effects on caloric and water intake, meal microstructure and locomotion were assessed, using an automated weighing system and telemetry in male rats with restricted 18‐h access to Western style diet. SIB 3 mg/kg reduced meal size and frequency, which suggests enhanced within‐ and postmeal satiety. Imiloxan (α2B‐AR), WB4101 (α1‐AR), SB‐224289 (5‐HT1B), and modestly BRL 44408 (α2A/D‐AR) attenuated SIB's effect on meal size, suggesting that α2B‐ and α1‐ARs and 5‐HT1B receptors mediate within‐meal satiety, with a modest role for α2A/D‐ARs. Only prazosin (α1/2B/2C‐AR) counteracted SIB's effect on meal frequency. At 3 mg/kg, SIB modestly increased locomotion. This effect was blocked by metergoline (5‐HT1/2/7), WB4101 (α1‐AR), and RX821002 (α2‐AR). Interestingly, the α2‐AR antagonists atipamezole and RX821002 enhanced SIB's effect on caloric intake, probably due to inverse agonistic actions at α2A‐autoreceptors that further enhanced release of NA that regulates caloric intake. Thus, an inverse agonist of presynaptic α2A‐ARs might beneficially enhance SIB's weight‐reducing effect and offer novel treatment for obesity. All in all, the present data supports the ARs and 5‐HT receptors involved in the effects of SIB on different aspects of caloric intake and locomotion.

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“…28,30,51,52 Rather than looking for a perfect reconstruction method, it might be worth looking at pathways that regulate food intake after total gastrectomy. The manipulation of these pathways by defined receptor agonist or antagonist treatments might be an alternative way to increase body weight after total gastrectomy, 18,43,53 possibly alleviating the sequelae of total gastrectomy for these patients.…”

Section: Regulation Of Food Intake After Total Gastrectomy In Ratsmentioning

confidence: 99%

Total Gastrectomy Severely Alters the Central Regulation of Food Intake in Rats

Zittel¹,

Glatzle²,

Müller³

et al. 2002

Annals of Surgery

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ObjectiveTo 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 DataTotal 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. MethodsThe 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. ResultsNeuronal 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. ConclusionsThe 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.Total gastrectomy is still a mainstay of gastric cancer treatment.1 It is followed by a variety of symptoms and impairments, commonly referred to as postgastrectomy syndromes.2 One important feature of the postgastrectomy syndromes is a considerable loss of body weight.3,4 The loss averages around 25% of preoperative body weight 4,5 and leaves 60% to 70% of patients permanently below ideal body weight. 3,6 While perioperative weight loss due to catabolic metabolism is generally followed by an anabolic phase 3 to 8 days postoperatively with body weight recovery, 7 this is not the case in gastrectomized patients, where weight loss and underweight frequently cause long-lasting morbidity. 4 -6,8 There is evidence that pancreatic insufficiency, resulting in malabsorption and impaired food utilization, contributes Correspon...

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Serotonin Receptor Blockade Increases Food Intake and Body Weight after Total Gastrectomy in Rats

Cited by 12 publications

References 61 publications

Postoperative Ghrelin Levels and Delayed Recovery from Body Weight Loss after Distal or Total Gastrectomy

Postoperative Ghrelin Levels and Delayed Recovery from Body Weight Loss after Distal or Total Gastrectomy

Inverse Agonism at α2A Adrenoceptors Augments the Hypophagic Effect of Sibutramine in Rats

Total Gastrectomy Severely Alters the Central Regulation of Food Intake in Rats

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