Role of Free Fatty Acids in Regulating Gastric Emptying and Gallbladder Contraction

Abstract

The limited effectiveness of orlistat, an inhibitor of gastrointestinal lipases, in inhibiting fat digestion is not completely understood. Therefore we studied the effect of orally and duodenally administered orlistat on gastric emptying, cholecystokinin (CCK) secretion, and gallbladder contraction. In healthy males, gastric emptying of solids and fat were quantified scintigraphically, gallbladder contraction by ultrasound and CCK release by radioimmunoassay. Three studies were performed: (1) oral and (2) duodenal orlistat with a fat-containing meal, and (3) duodenal orlistat with a fat-free meal. Gastric emptying rates of solids and fat (T_50% accelerated by 16 and by 22%, p< 0.05, respectively) were significantly faster after duodenal perfusion of orlistat; gallbladder contraction and CCK release were reduced under these conditions (p < 0.005, respectively). With oral orlistat no significant effect was documented on these parameters. We conclude that fat hydrolysis is essential in the regulation of fat-induced gastric emptying and gallbladder contraction.

Diet: Friend or Foe of Enteroendocrine Cells: How It Interacts with Enteroendocrine Cells

“…In addition, the administration of a CCK-1R antagonist in healthy subjects almost attenuated the long-chain fatty acid-induced PYY secretion, suggesting that the induction of PYY secretion by long-chain fatty acids is partly through CCK stimulation (60). As per the present data, it would be interesting to study fatty acid induction in PYY secretion in isolated L cells to determine whether CCK alone is responsible for the long-chain fatty acid-induced response in PYY.…”

“…For instance, pancreatic lipase insufficiency is associated with a poor CCK response to TG but a normal response to oleic acid (48,54,59). In addition, intestinal infusion of the lipase inhibitor, orlistat, together with TG virtually abolishes the postprandial release of CCK (60,61). The length of the fatty acid carbon chain also determines CCK release.…”

Long-chain fatty acid sensing in the gastrointestinal tract

“…The pancreatic lipase inhibitor Orlistat prevents gallbladder emptying, satiety and CCK secretion, indicating that only free fatty acids are sensed and not intact triacylglycerols [5,6]. Furthermore, topical local anaesthetic application attenuates the feeding response to long-chain fat [7].…”

“…However, previous studies demonstrated that fatty acids alone were adequate to induce gall-bladder contraction, pancreatic exocrine secretion and delayed gastric emptying [3,4]. These studies suggested that a chain length of more than eight carbon atoms was necessary.The pancreatic lipase inhibitor Orlistat prevents gallbladder emptying, satiety and CCK secretion, indicating that only free fatty acids are sensed and not intact triacylglycerols [5,6]. Furthermore, topical local anaesthetic application…”

Stomach and Gallbladder under Fat Control?

“…Still, it seems that the meal proportion of carbohydrate and protein have only minor effects on gastric emptying, prompting more focus on the impact of fat. With fat in the stomach or duodenum, delay and also acceleration of gastric emptying have been reported, depending on the utilized experimental setting [1] .In this issue of Digestion , Degen et al [4] shed more light onto this somehow controversial area while looking at it from a different perspective. They addressed the question whether fat hydrolysis is mandatory for the ability of lipid to trigger regulation of upper gastrointestinal function such as gallbladder contraction and inhibition of gastric emptying.…”