Diunsaturated Aldehyde, trans,trans-2,4-Decadienal in the Intestinal Lumen Suppresses Gastric Emptying through Serotonin Signaling in Rats

Abstract

We recently demonstrated that a diunsaturated aldehyde, trans,trans-2,4-decadienal (2,4-decadienal), potently stimulated secretion of cholecystokinin in the enteroendocrine cell line. Gut hormones such as cholecystokinin and serotonin play critical roles in reducing postprandial gastric emptying. In the present study, we first demonstrated that oral administration of 2,4-decadienal (50-100 mg/kg) reduced gastric emptying rate in rats, assessed by both the acetaminophen absorption test and the phenol red recovery method. In contrast, saturated aldehyde, alcohol, and fatty acids having the same chain length as 2,4-decadienal did not affect the gastric emptying rate. Duodenal administration of 2,4-decadienal potently reduced gastric emptying rate, but intraperitoneal administration did not. Furthermore, the gastric inhibitory effect of 2,4-decadienal was attenuated by treatment with a serotonin receptor antagonist. These results demonstrated that 2,4-decadienal in the small intestinal lumen has a potent inhibitory effect on gastric emptying, possibly through stimulation of the serotonin-producing enteroendocrine cells.

Enterochromaffin 5-HT cells – A major target for GLP-1 and gut microbial metabolites

“…In relation to our observation that GLP-1 stimulates 5-HT secretion from EC cells, it is interesting that antagonism of 5HT3 receptors has been shown to abolish glucose- and flavor-induced suppression of gastric emptying [17] , [63] , indicating that 5-HT secretion from the EC cells and subsequent stimulation of 5HT3 receptors on vagal afferents possibly could be involved in this physiological mechanism. Thus, 5-HT secretion from EC cells could either add to or act in synergy with the suppression of gastric emptying by endogenous GLP-1 or it could be the mechanism through which endogenous, intestinal GLP-1 and perhaps also some GLP-1 mimetics affect gastric emptying.…”

Novel Mechanism of Fatty Acid Sensing in Enteroendocrine Cells: Specific Structures in Oxo‐Fatty Acids Produced by Gut Bacteria Are Responsible for CCK Secretion in STC‐1 Cells via GPR40

“…The effect of oral administration of the oxo‐fatty acids on gastric emptying rate was examined in vivo by oral coadministration of a test agent and an absorbable marker, acetaminophen ( Figures A,C, B), or a nonabsorbable marker, phenol red (Figure B). An unsaturated aldehyde 2t,4t‐decadienal, used as a positive control, significantly reduced the appearance of acetaminophen in the peripheral vein (Figure A) and the gastric emptying rate (Figure B). At the same dose (25 mg kg −1 ), 13‐oxo‐9c,15c‐18:2 administration resulted in significantly lower acetaminophen levels after 15 min (Figure A), and lower gastric emptying rates (Figure B), while 10‐oxo‐11t‐18:1 administration had no effect compared to the control (vehicle) treatment.…”

“…We expected that the fatty acids would exert an inhibitory effect on gastric emptying in vivo, as delaying gastric emptying is a distinct physiological function of several gut hormones including CCK . Although the effect was relatively smaller than that of 2t,4t‐dacadienal at the same weight dose (25 mg kg −1 ), the oral administration of 13‐oxo‐9c,15c‐18:2 decreased the gastric emptying rate as evaluated by two independent methods, while 10‐oxo‐11t‐18:1 did not (Figure A,B). Because the fatty acids were orally administered, the failure of 10‐oxo‐11t‐18:1 to inhibit gastric emptying could be due to insufficient delivery of active form fatty acids to the site of action (possibly the small intestinal lumen).…”

“…Acetaminophen (100 mg kg −1 body weight) was added as an absorbable marker to assess the gastric emptying rate . A diunsaturated aldehyde, trans,trans ‐2,4‐decadienal (2t,4t‐decadienal, Tokyo Chemical Industry Co., Ltd., Tokyo, Japan) was employed as a positive control, as it has an inhibitory effect on gastric emptying in rats …”

Potential adverse health effects of dietary lipid oxidation products

“…Gomes et al (2002) found that acrolein (6 mg/kg) administration by gavage for 70 days in rats induced erosion, hyperplasia and hyperkeratosis in the glandular mucosa of the stomach or in the forestomach. Oral administration of tt-DDE (800 mg/kg) by gavage for 3 months can induce forestomach ulceration and diarrhea, and inhibit gastric emptying rate in rats through inducing cholecystokinin (CCK) secretion in rats (Chan, 2011;Hira et al, 2015). More recently, Rom et al (2017) reported that intake of acrolein (3 mg/kg/day) for 1 month induced a major shift in the gut microbiota composition in atherosclerotic ApoE-/-mice, including a significant phylum-level change with increased Firmicutes and decreased Bacteroidetes.…”