Rats were made obese by VMH knife-cuts and then a 5 or 10 cm segment of terminal ileum was transposed to the duodenum. After surgery, the food moved from the stomach into upper duodenum and then traveled through the transposed ileal segment to lower duodenum and continued down the remaining normal digestive tract. Ileal transposition caused a significant reduction in food intake and a substantial loss of body weight. There was no difference in weight loss with 5 and 10 cm ileal transpositions in obese rats, but weight loss was much less in lean rats. Weight loss was accompanied by a considerable loss in dissectable body fat and an increase in the actual weight of the pancreas and small intestine. These changes are probably caused by the unusual stimulation of a short segment of terminal ileum with undigested food and pancreatic enzymes and may have been mediated by the release of ileal hormones. Changes in plasma levels of metabolites, intracellular enzymes, and protein are presented and the importance of this surgery for the treatment of human obesity is evaluated.
Cannabinoid (CB)(1) receptors are present throughout the nervous system, including several areas implicated in the control of food intake. Central and peripheral administration of CB(1) agonists increase food intake while CB(1) receptor antagonists reduce food intake. However, in some previous studies, tolerance to the anorectic effects of CB(1) antagonists develops within days. To further delineate the role of endogenous cannabinoid signaling in energy intake, we studied the effects of the CB(1) antagonist AM 251 (1.25, 2.5 and 5 mg/kg ip), the anandamide membrane transporter inhibitor VDM 11 (10 mg/kg ip), and the CB(1) agonists anandamide (1 mg/kg ip), and methanandamide (1 mg/kg ip), on food intake. A single administration of the CB(1) antagonist AM 251 significantly reduced food intake for a total of 6 days (P<.05). Reductions in food intake brought about by AM 251 were accompanied by reductions in weight gain for 6 days (P<.05). Contrary to expectations, VDM 11 did not increase food intake in this study. Anandamide was also unable to increase food intake; however, the more stable agonist methanandamide significantly increased food intake 3 h after administration (P<.05). These results support the role of CB(1) receptor antagonists in the treatment of obesity and suggest that the anorectic effect of AM 251 may last longer than previously reported.
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