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Review
. 2013 May;91(5):1991-2000.
doi: 10.2527/jas.2013-6331.

Digestive physiology of the pig symposium: intestinal bile acid sensing is linked to key endocrine and metabolic signaling pathways

D Burrin  1 , B Stoll, D Moore
Affiliations
Review

Digestive physiology of the pig symposium: intestinal bile acid sensing is linked to key endocrine and metabolic signaling pathways

D Burrin et al. J Anim Sci. 2013 May.

Abstract

Bile acids have historically been considered to mainly function in cholesterol homeostasis and facilitate fat digestion in the gastrointestinal tract. Recent discoveries show that bile acids also function as signaling molecules that exert diverse endocrine and metabolic actions by activating G protein-coupled bile acid receptor 1 (GPBAR1/G-protein-coupled bile acid receptor 1 or TGR5), a membrane G protein-coupled receptor, and farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily. These bile acid sensing receptors are expressed in intestinal epithelial cells, TGR5 in enteroendocrine cells and FXR in enterocytes, which line the mucosa of gut lumen. A dominant effect of intestinal FXR activation by bile acids is secretion of fibroblast growth factor (FGF) 19, a novel enterokine that functions as a central enterohepatic signal to maintain bile acid homeostasis in the liver. Activation of TGR5 on enteroendocrine cells stimulates secretion of glucagon-like peptides (GLP)-1 and -2, which function, respectively, as the major incretin hormone involved in glucose homeostasis and key trophic hormone in intestinal adaptation and growth in response to food ingestion. The biological actions induced by bile acid activation of intestinal FXR and TGR5 have important therapeutic implications for the pathogenesis and treatment of several metabolic diseases, such as cholestasis and diabetes. This review highlights these new developments in the biology of intestinal bile acid sensing and metabolic function and discusses the potential implications for the health and agricultural production of domestic swine.

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Figures

Figure 1
Figure 1
Enteroendocrine cell morphology. The left panel shows an electron micrograph image of an enteroendocrine cell. Note the top apical brush border and lower electron-dense secretory granules marked with black arrows. The right panel shows staining of an enteroendocrine cell in neonatal pig ileum tissue using immunohistochemical labeling with a polyclonal antibody directed against the glucagon-like peptides (GLP)-2 (Image courtesy of C. Bauchart-Thevret, USDA Children’s Nutrition Research Center, and Baylor College of Medicine, Houston, TX). Note the apical brush border to left and basolateral surface on right marked with black arrows. Electron micrograph image was reproduced from (Meschere, 2010) with permission.
Figure 2
Figure 2
Intestinal epithelial cell bile acid (BA) sensing. Illustration shows TGR5 receptor signaling in enteroendocrine cells and farnesoid × receptor (FXR) signaling in enterocytes. Signaling mechanisms for apical membrane-associated TGR5 receptor in enteroendocrine cells involve activation of G protein coupled pathways with adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP), and calcium channels that trigger secretion of glucagon-like peptides (GLP)-1 and GLP-2 into the portal vein. Signaling mechanism for FXR located in the nucleus of enterocytes triggers secretion of fibroblast growth factor (FGF) 19 into the portal vein. Conjugated bile acids are transported into ileal enterocytes by the apical sodium-dependent bile acid transporter (ASBT) and bind intracellular ileal lipid binding protein (ILBP) before export into the portal vein by the organic solute transporter (OST)..
Figure 3
Figure 3
Bile acid-induced gut hormone secretion. Illustration shows differential activation of enterocyte fibroblast growth factor (FGF) 19 secretion and enteroendocrine glucagon-like peptides (GLP)-1 and GLP-2 secretion by luminal bile acids in the small intestine. The target for FGF19 action is mainly the liver and negative feedback of enterohepatic bile acid secretion. The targets for GLP-1 and GLP-2 action are mainly the pancreas β cell and the gastrointestinal mucosa, respectively.
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