Bile Acids Induce Glucagon-Like Peptide 2 Secretion with Limited Effects on Intestinal Adaptation in Early Weaned Pigs

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 β-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, did not result in improved intestinal growth, morphology, or inflammation during the postweaning degenerative phase.

Glucagon-like peptide 2 and its beneficial effects on gut function and health in production animals

“…Stimulation of GLP-2 secretion through administration of a specific bile acid (presumably through activation of the receptor TGR5) also increased size of the ileum but did not alter gut morphology or cell proliferation within the villi and crypts [26]. In this study, some associated intestinal inflammation was observed at the administered dose of bile acid, which the authors suggested may have negated other growth-promoting effects of GLP-2 on the gut.…”

“…This primarily was due to the discovery that enteric peptides, such as glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide, and peptide YY, play key roles in the regulation of appetite, energy metabolism [15][16][17], and gut function [18][19][20], making them targets for managing prevalent human diseases of obesity and diabetes. As knowledge has continued to grow, the potential to improve gut function and health of food animals through the manipulation of enteric peptide secretion has become increasingly more apparent [21][22][23][24][25][26].…”

COMPARATIVE GUT PHYSIOLOGY SYMPOSIUM: Comparative physiology of glucagon-like peptide-2: Implications and applications for production and health of ruminants12

“…Second, the receptor TGR5 is stimulated by bile acids, and its activation has been shown to stimulate GLP-1 release in a mouse enteroendocrine cell line (Katsuma et al, 2005) and GLP-2 secretion in perfused rat duodenum (Inoue et al, 2012). Furthermore, it is through this receptor that feeding of the bile acid, chenodeoxycholic acid, was believed to stimulate GLP-2 release in early weaned pigs (Ipharraguerre et al, 2013).…”

“…Glucagon-like peptide-2 (GLP-2) has been a target of investigation for improving nutrient absorption and production efficiency of poultry (Hu et al, 2010) and livestock Sigalet, 2012;Ipharraguerre et al, 2013) because of its effects on the intestinal mucosa. Treatment of nonruminants with GLP-2 stimulates intestinal crypt cell proliferation, reduces apoptosis and inflammation in gut mucosal epithelium, and enhances nutrient absorption and gut integrity after injury (Lovshin and Drucker, 2000;Burrin et al, 2003;Drucker, 2005).…”

The effect of tributyrin supplementation to milk replacer on plasma glucagon‐like peptide 2 concentrations in pre‐weaning calves

“…Glucagon-like peptide-2 (GLP-2), one of the gut-derived peptides, has been a target of research for ameliorating nutrient absorption and production efficiency of livestock (Burrin, Stoll, & Guan, 2003b;Ipharraguerre et al, 2013;Sigalet, 2012). The GLP-2 is produced by enteroendocrine L cells of the gastrointestinal tract (GIT), primarily from the distal intestine in response to nutrient intake (Burrin, Stoll, et al, 2003b), and plays a role in stimulation of intestinal growth in non-ruminants (Drucker, Erlich, Asa, & Brubaker, 1996;Hartmann et al, 2000;Kato, Yu, & Schwartz, 1999).…”