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Title: Bile acids induce glucagon-like peptide 2 secretion with limited effects on intestinal adaptation in early weaned pigs

Author
item IPHARRAGUERRE, IGNACIO - Lucta
item TEDO, GEMMA - Lucta
item MENOYO, DAVID - Polytechnic University Of Madrid
item DE DIEGO CABERO, NURIA - Polytechnic University Of Madrid
item HOLST, JENS - University Of Copenhagen
item NOFRARIAS, MIQUEL - Autonomous University Of Barcelona
item MEREU, ALESSANDRO - Lucta
item Burrin, Douglas - Doug

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/5/2013
Publication Date: 12/1/2013
Citation: Ipharraguerre, I.R., Tedo, G., Menoyo, D., De Diego Cabero, N., Holst, J.J., Nofrarias, M., Mereu, A., Burrin, D.G. 2013. Bile acids induce glucagon-like peptide 2 secretion with limited effects on intestinal adaptation in early weaned pigs. Journal of Nutrition. 143(12):1899-1905.

Interpretive Summary: In the setting of pig production, when piglets are weaned from their mothers the change in environment and diet induces stress that causes a loss of appetite and delay in intestinal development. The delayed intestinal development increases the risk for infection and reduces normal growth. Our previous studies discovered that the normal ingestion of food stimulates secretion of an important intestinal growth hormone called glucagon-like peptide 2 (GLP-2). We also recently showed that feeding small amounts of bile acids that are normally made by the liver and involved in fat digestion, also increases the secretion of this potent intestinal hormone. We designed a study to test whether giving small amounts of bile acids in the diet of piglets in the first week after weaning from the mothers would stimulate the secretion of GLP-2 and lead to improved intestinal growth and development. We found that it did increase GLP-2 secretion compared to the control group, it did not significantly improve intestinal growth and development. This study shows novel evidence that bile acids can be used as a nutritional approach to increase GLP-2 secretion. Further studies are warranted to establish whether dietary bile acid feeding can be used to improve intestinal function in weanling pigs.

Technical Abstract: Early weaning is a stressful event characterized by a transient period of intestinal atrophy that may be mediated by reduced secretion of glucagon-like peptide (GLP) 2. We tested whether enterally fed bile acids or plant sterols could increase nutrient-dependent GLP-2 secretion and improve intestinal adaptation in weanling pigs. During the first 6 d after weaning, piglets were intragastrically infused once daily with either deionized water (control), chenodeoxycholic acid (CDC; 60 mg/kg body weight), or beta-sitoesterol (BSE; 100 mg/kg body weight). Infusing CDC increased plasma GLP-2 ("P" < 0.05) but did not affect plasma GLP-1 and feed intake. The intestinal expression of glucagon-like peptide 2 receptor, sodium-dependent bile acid transporter, farnesoid X receptor, and guanosine protein–coupled bile acid receptor genes were not affected by CDC treatment. The intragastric administration of CDC did not alter the weight and length of the intestine, yet increased the activation of caspase-3 in ileal villi ("P" < 0.02) and the expression of interleukin 6 ("P" < 0.002) in the jejunum. In contrast, infusing BSE did not affect any of the variables that were measured. Our results show that the enteral administration of the bile acid CDC potentiates the nutrient-induced secretion of endogenous GLP-2 in early-weaned pigs. Bile acid–enhanced release of GLP-2; however, it did not result in improved intestinal growth, morphology, or inflammation during the postweaning degenerative phase.