Vagal afferent responses to fatty acids of different chain length in the rat

The role of cholecystokinin (CCK) in the effect of dietary lipid on proxima l gastrointestinal function and satiety is controversial. Recent work sugge sts that fatty acid chain length may be a determining factor. We investigat ed the mechanism by which long- and short-chain fatty acids activate jejuna l afferent nerves in rats. Whole mesenteric afferent nerve discharge was re corded in anaesthetized male Wistar rats during luminal perfusion of saline , sodium oleate, and sodium butyrate (both 10 mM). Both fatty acids evoked characteristic afferent nerve responses, distinct from the mechanical respo nse to saline, that were abolished in rats following chronic subdiaphragmat ic vagotomy. The effect of oleate was abolished by the CCK-A receptor antag onist Devazepide (0.5 mg/kg), whereas the effect of butyrate persisted desp ite pretreatment with either Devazepide or a combination of the calcium cha nnel inhibitors nifedipine (1 mg/kg) and the omega -conotoxins GVIA and SVI B (each 25 mug/kg). In summary, long- and short-chain fatty acids activate intestinal vagal afferents by different mechanisms; oleate acts via a CCK-m ediated mechanism and butyrate appears to have a direct effect on afferent terminals.