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Slowing of transit through the proximal small intestine by fat in the distal gut is termed the ileal brake. Intravenous naloxone, an opioid receptor antagonist, abolished the fat-induced ileal brake, suggesting that an endogenous opioid pathway may be involved in this response. To test the hypothesis that slowing of intestinal transit by fat in the distal half of the gut depends on an opioid pathway located on the efferent limb of this response, we compared intestinal transit in dogs equipped with duodenal and midgut fistulas while naloxone was either compartmentalized with oleate to the distal half of the gut or with buffer to the proximal half of the gut. We found that intestinal transit depended on the perfusion conditions (P<0.00001). Specifically, compared with ileal brake (marker recovery of 35.7+/-7.4%), intestinal transit was accelerated when naloxone was delivered into the proximal half of the gut (76.2+/-5.2%) (P<0.005) but not the distal half of the gut (29.4+/-5.4%). We conclude that slowing of intestinal transit by fat in the distal half of the gut depends on an opioid pathway located on the efferent limb of the ileal brake.

Patients with fat intolerance complain of early satiety, bloating, nausea, and vomiting. Since these symptoms are similar to those of patients with postgastrectomy dumping syndrome, we hypothesized that fat intolerance may be associated with early, rapid gastric emptying. Using a three-meal gastric emptying study, we compared gastric emptying in nine patients with a history of fat intolerance and nine normal volunteers. On three separate days, 500-ml radiolabeled test meals containing 0, 15, or 60 g of fat were studied. The percentages of the test meal emptied at 15 and 60 min were analyzed by repeated measures two-way ANOVA. At 15 min (p < 0.05) but not 60 min, gastric emptying was faster in patients than normals. Gastric emptying at 15 min (p < 0.001) and 60 min (p < 0.001) depended on the dose of fat. We conclude that fat intolerance is associated with early, rapid gastric emptying.

Fat in the proximal and distal gut inhibits intestinal transit as the jejunal brake and the ileal brake. It is unknown, however, whether the intestinal transit response to fat in the proximal vs distal gut is different. Since surgical removal of the distal small intestine induced faster transit and greater steatorrhea than removal of the proximal small intestine, we hypothesized that the ileal brake inhibited intestinal transit more potently than the jejunal brake. In six dogs equipped with duodenal (10 cm from pylorus) and midintestinal (160 cm from pylorus) fistulas, we compared intestinal transit across an isolated 150-cm test segment (between fistulas), while 0 (buffer), 15, 30, or 60 mM oleate was delivered into either the proximal (between fistulas) or the distal (beyond the midintestinal fistula) half of the gut. The half of the gut not receiving oleate was perfused with buffer. Buffer perfused into both the proximal and the distal half of the gut served as the control. A meal was administered and diverted completely out of the duodenal fistula so that the studies were all done in the fed state. Intestinal transit was measured by counting for the recovery of a radioactive marker from the temporarily diverted output of the midintestinal fistula. We found that (1) intestinal transit was inhibited more potently by oleate in the distal than in the proximal half of the gut (region effect; P < 0.01), (2) oleate inhibited intestinal transit in a load-dependent fashion (dose effect; P < 0.05), and (3) load-dependent inhibition of intestinal transit by oleate depended on the region of exposure (interaction between load and region; P < 0.01). We conclude that intestinal transit is more potently inhibited by fat-induced ileal than jejunal brake.

Since the intubation study of B. Borgstrom, A. Dahlqvist, and G. Lundh (J. Clin. Invest. 36: 1521-1536, 1957) in humans, the completion of fat absorption within the proximal small intestine has been widely accepted. Based on this report, it has been assumed that the distal small intestine is exposed to fat only in the setting of pathology. This concept may be flawed, since completeness of fat absorption was calculated from the recovery of a water-soluble marker but the aqueous phase is now known to move independently from fat. To reexamine the question of whether fat absorption is complete by midgut, we measured the recovery of a fat-specific marker, 99mTc-thiocyanate, in a canine model equipped with duodenal and midgut fistulas. The fistulous output allowed for the measurement of the amount of fat entering the small intestine and the amount of fat entering the distal one-half of the small intestine. Emulsion meals containing 15 or 60 g of corn oil were tested. The importance of fat exposure of the distal one-half of the small intestine was further confirmed by comparing the fistulous fat recovery under two different patterns of exposure [allowing (ALL) or denying (150 cm) access to the distal small intestine]. We found that fat recovery depended on 1) the dose of fat (15 vs. 60 g; P < 0.0005), 2) the pattern of exposure (150 cm vs. ALL; P < 0.01), and 3) the fistulous position (duodenal vs. midgut; P < 0.005). Specifically, under a 150-cm exposure pattern, whereas 8.8 +/- 1.8 g (means +/- SE) of fat emptied into the duodenum after the 15-g fat meal, 32.6 +/- 3.2 g emptied after the 60-g fat meal. Correspondingly, although 3.5 +/- 1.5 g of fat were recoverable from the midgut fistulous output after the 15-g meal, a much larger amount, 17.1 +/- 5.6 g of fat, was recoverable and therefore not absorbed by the proximal one-half of the small intestine after the 60-g meal. The amount of fat recovery at each fistula was reduced when chyme was allowed access to the whole gut (by triggering fat-induced ileal brake). We conclude that the intestinal length required for fat absorption depends on the load of fat in the meal so that, even after usual meals, absorption of fat is not complete by midgut.

Optimal absorption of fat requires adequate time of contact with the absorptive sites of the small intestine. In order to prevent steatorrhea, intestinal transit must be slowed in response to the fat that has emptied into the small intestine. Intestinal transit is known to be inhibited by fat in the ileum via the ileal brake. This response has suggested that the regulation of intestinal transit is a function of the distal small intestine. However, clinical observations suggest that the ileal brake is not the only control mechanism for intestinal transit. In short bowel patients with resection of the ileum, the proportion of fecal fat recovery remained constant even after the fat intake was increased threefold. In these patients, optimal fat absorption based on the slowing of intestinal transit must have been triggered by an inhibitory mechanism located outside of the distal small intestine. To test the hypothesis that fat in the proximal small intestine inhibited intestinal transit, we compared intestinal transit during perfusion of the proximal half of the small intestine with 0 (buffer only), 15, 30, or 60 mM oleate in dogs equipped with duodenal and mid-intestinal fistula. Intestinal transit across a 150-cm test segment (between fistulas) was measured by counting for the recovery of a radioactive marker in the output of the mid-intestinal fistula during the last 30 min of a 90-min perfusion. We found that oleate inhibited intestinal transit in a load-dependent fashion (P < 0.005). Specifically, while the mean cumulative recovery of the transit marker was 95.5% during buffer perfusion, the recovery decreased when 15 mM (64.3%), 30 mM o(54.7%), or 60 mM oleate (38.7%) was perfused into the proximal half of the small intestine. We conclude that fat in the proximal small intestine inhibits intestinal transit as the jejunal brake.