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differential action of tgr5 agonists on glp-2 secretion and promotion of intestinal adaptation in a piglet short-bowel model

category: feed additives

date:july 2018

authors: sen lin, barbara stoll, jason robinson, juan marini, jose pastor, ignacio r. ipharraguerre, jens j. holst, bolette hartmann, stephanie cruz, patricio lao, oluyinka olutoye, zhengfeng fang, douglas burrin

book/journal:american society of animal science meeting, july 2018, vancouver, canada


we previously showed that feeding bile acids can induce glucagon-like peptide 2 (glp-2) secretion and intestinal growth in parenteral nutrition-fed (pn) piglets. we hypothesize that bile acids function as agonist for the g protein-coupled bile acid receptor 1 (tgr5) expressed in enteroendocrine l cells to induce glp-2 secretion. our in this study was to test whether natural tgr5 agonists can increase glp-2 secretion and intestinal adaptation in piglet short bowel model. in study 1, 24 neonatal piglets were pn-fed and given oral gavage with one of four tgr5 treatments to measure acute glp-2 secretion. in study 2, neonatal piglets underwent either 80% midjejunoileal resection or transection surgery and receive either 1) transection, 2) resection, 3) resection 10 mg ursolic acid (ua), 4) resection 60 mg compound r071. in study 1, oral gavage with ua, but not r071, increased glp-2 secretion (p < 0.05). in study 2, compared to transection, remnant ileum villus height, crypt cell proliferation, and plasma glp-2 secretion was increased (p < 0.05) by resection but not further stimulated by ua or r071. bile acid profiling showed that ua and r071 increased (p < 0.05) conjugated hca and hdca level in liver and decreased (p < 0.05) conjugated hca, hdca and cdca level in ileum. resection tended (p=0.08) to increase, while ua decreased liver il-1β expression. we conclude that oral tgr5 agonists differentially increased glp-2 secretion in healthy pn-fed pigs, but did not augment glp-2 secretion or intestinal adaptation after resection in short-bowel piglets. we found that tgr5 agonists altered bile acid homeostasis and had anti-inflammatory actions in liver in short-bowel piglets.