Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids |
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| Authors: | Courtney B Ferrebee Paul A Dawson |
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| Institution: | aDepartment of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Emory University, Atlanta, GA 30322, USA;bMolecular Medicine Graduate Program, Wake Forest School of Medicine, Winston-Salem, NC 27153, USA |
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| Abstract: | The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size, and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as farnesoid X nuclear receptor (FXR) and the G-protein-coupled bile acid receptor (TGR5).KEY WORDS: Bile acids, Liver, Intestine, Transporters, Lipid metabolism, Energy homeostasisAbbreviations: ACCII, acetyl-CoA carboxylase 2; APO, apolipoproteins; ASBT, apical sodium-dependent bile acid transporter; BSEP, bile salt export pump; CYP7A1, cholesterol 7α-hydroxylase; DIO2, deiodinase 2; FAS, fatty acid synthase; FGF, fibroblast growth factor; FOXO1, forkhead box protein O1; FGFR4, fibroblast growth factor receptor 4; FXR, farnesoid X-receptor; G6Pase, glucose-6-phosphatase; GLP-1, glucagon-like polypeptide-1; HNF4α, hepatocyte nuclear factor 4 alpha; IBABP, ileal bile acid binding protein; LDL, low density lipoprotein; NTCP, Na+-taurocholate transporting polypeptide; OATP, organic anion transporting polypeptide; OST, organic solute transporter; PEPCK, phosphoenolpyruvate carboxykinase; PGC1α, peroxisome proliferator-activated receptor gamma coactivator 1 alpha; PPAR, peroxisome proliferator-activated receptor; SHP, small heterodimer partner; SREBP1c, sterol regulatory element binding protein-1c; T4, thyroid hormone; TGR5, G-protein-coupled bile acid receptor; VLDL, very low density lipoprotein |
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