Slowing of intestinal transit by fat depends on naloxone-blockable efferent, opioid pathway

Abstract

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.

Slowing intestinal transit by PYY depends on serotonergic and opioid pathways

“…The doses of ondansetron and naloxone were selected on the basis of the previously tested dose response of these agents (32,35). Doses used in this study have been shown to reverse the fat-induced ileal brake (32,59) and the fatinduced jejunal brake (32,35). Both ondansetron (32) and naloxone (59) were also previously shown to have no independent accelerating effect on intestinal transit of buffer.…”

“…Because the luminal content of the proximal and distal intestinal segments were not in continuity, this observation indicated that the fat-induced ileal brake occurred via a reflex, whereby the distal segment exposed to fat served as the afferent limb of the reflex and the proximal segment in which intestinal transit was measured served as the efferent limb. We also showed that delivering ondansetron (a 5-H 3 receptor antagonist) (32) or naloxone (a nonspecific opioid receptor antagonist) (59) into the proximal but not distal intestinal segment reversed the fat-induced ileal brake to localize the serotonergic (32) and opioid (59) pathways involved in the fat-induced ileal brake response to the efferent limb of the slowing reflex. In this study, we will test the hypothesis that the slowing of intestinal transit by PYY may depend on similar pathways.…”

Dose–response effects of a novel fat emulsion (Olibra™) on energy and macronutrient intakes up to 36 h post-consumption

“…These outlying data may be a result of the mis-reporting of food intakes, since self-reported food intakes are well recognised to be susceptible to underreporting (Livingstone et al, 1990;Black et al, 1993). Dose -response effect of Olibra TM AA Burns et al It has been suggested that the observed lowering in energy and macronutrient intakes following the consumption of Olibra TM fat was a result of the 'ileal-brake' mechanism (Burns et al, 2000(Burns et al, , 2001, ie the inhibition of upper gastrointestinal functions elicited by the presence of unabsorbed nutrients in the ileum (Zhao et al, 2000). The 'ileal-brake' appears to be related to the release of one or more peptide hormones from the distal intestine.…”

No appetite efficacy of a commercial structured lipid emulsion in minimally processed drinks

“…This is a satiety response stimulated by the presence of slowly digested nutrients (fat in this case) in the distal small intestine, 5,23 and involves an increase in the release of the satiety hormone GLP-1. 1 --4 Not just GLP-1, but also CCK, 24 PYY 25 and the opioid system 26 have been implicated in the ileal brake mechanism. Amounts of fat as a low as 3 g delivered directly to the ileum have been shown to trigger this mechanism, 26 suggesting that such effects of a structured food emulsion are at least plausible.…”

“…1 --4 Not just GLP-1, but also CCK, 24 PYY 25 and the opioid system 26 have been implicated in the ileal brake mechanism. Amounts of fat as a low as 3 g delivered directly to the ileum have been shown to trigger this mechanism, 26 suggesting that such effects of a structured food emulsion are at least plausible. Additionally, a 45-min prolonged oro-caecal transit time following the ingestion of Fabuless has been reported, 27 although we have previously challenged those findings.…”