Upper gastrointestinal motility, gut hormones and food intake : a study in normal weight and obese humans

Sammanfattning: The regulation of food intake in man is complex and poorly understood. The main aim of the present study was to investigate how a rapid stimulation of the distal small bowel with nutrients influences upper gastrointestinal motility, some gut peptides and food intake in man. Therefore, fasting small bowel motility, gastric emptying, plasma and intraduodenal levels of some neuropeptides, plasma levels of cholecystokinin (CCK), motilin (MOT ), neurotensin (NT ), glucagon like peptide- I (GLP- 1 ) and peptide YY (PYY) were studied in lean, obese, and obese subjects nine months and 20 years after jejunoileal bypass (JIB). Plasma levels of MOT, but not the studied neuropeptides showed a cyclic variation in synchrony with the different phases of the migrating motor complex (MMC). In contrast, intraduodenal levels of somatostatin, vasoactive intestinal peptide, substance P and calcitonin gene-related peptide showed a peak immediately before or at phase III of the MMC. No difference was found in fasting motility between obese and lean subjects. After JIB, there were fewer phase III recorded during 5 hours than before surgery. Of the gut peptides studied only fasting levels of PYY were elevated suggesting that PYY may be involved in the regulation of fasting motility in man after JIB. The rate of gastric emptying was faster in obese subjects than in lean controls. The obese subjects also had a decreased postprandial response of plasma CCK and GLP- I. Whether the faster rate of gastric emptying and weaker GLP-1 and CCK response in the obese subjects is a cause or consequence of the obese state is not clear. After JIB the rate of gastric emptying was slower than before surgery and similar to that in lean controls. Plasma levels of GLP-l, NT and PYY were elevated after surgery suggesting that an ileal brake on upper gut motility is in effect after JIB. ln subjects operated with JIB a mean of twenty years earlier, both fasting and postprandial plasma levels of all the gut peptides studied were higher than in lean subjects and in subjects nine months after JIB. However, no difference was seen in the rate of gastric emptying between non-operated obese and obese subjects 20 years after JIB. This suggests that a down-regulation of the ileal brake occurs after long time stimulation of the distal ileum with nutrients. All the obese subjects lost weight after surgery and showed a decreased energy intake, diminished desire to eat, and diminished preference for high carbohydrate foods. Thus, it is likely that a rapid stimulation of the ileum influences food intake by elevating gut peptide levels and by inhibiting upper gastrointestinal motility. The fewer phase III of the MMC and slower rate of gastric emptying may contribute to increased satiety by a stronger and longer activation of mechano- and chemoreceptors in the stomach and upper small intestine. In addition, the postprandial elevated distal gut peptide concentrations may directly inhibit the feeding centers in the brain and decrease food intake.