title: The roles of bile acids and sphingosine-1-phosphate signaling in the hepatobiliary diseases.
abstract: Based on research carried out over the last decade, it has become increasingly evident that bile acids act not only as detergents, but also as important signaling molecules that exert various biological effects via activation of specific nuclear receptors and cell signaling pathways. Bile acids also regulate the expression of numerous genes encoding enzymes and proteins involved in the synthesis and metabolism of bile acids, glucose, fatty acids, and lipoproteins, as well as energy metabolism. Receptors activated by bile acids include, farnesoid X receptor α, pregnane X receptor, vitamin D receptor, and G protein-coupled receptors, TGR5, muscarinic receptor 2, and sphingosine-1-phosphate receptor (S1PR)2. The ligand of S1PR2, sphingosine-1-phosphate (S1P), is a bioactive lipid mediator that regulates various physiological and pathophysiological cellular processes. We have recently reported that conjugated bile acids, via S1PR2, activate and upregulate nuclear sphingosine kinase 2, increase nuclear S1P, and induce genes encoding enzymes and transporters involved in lipid and sterol metabolism in the liver. Here, we discuss the role of bile acids and S1P signaling in the regulation of hepatic lipid metabolism and in hepatobiliary diseases.
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata City 951-8510, Japan mnagahashi@med.niigata-u.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nagahashi
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata City 951-8510, Japan.
authors.forename: Kizuki
authors.initials: K
authors.lastname: Yuza
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata City 951-8510, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirose
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata City 951-8510, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, VA 23298.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ramanathan
authors.affiliation: Surgical Oncology and Molecular and Cellular Biology Roswell Park Cancer Institute, Buffalo, NY 14263.
authors.forename: Nitai C
authors.initials: NC
authors.lastname: Hait
authors.affiliation: Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University School of Medicine, Richmond, VA 23298 and McGuire Veterans Affairs Medical Center, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23224.
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Hylemon
authors.affiliation: Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University School of Medicine, Richmond, VA 23298 and McGuire Veterans Affairs Medical Center, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23224.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Breast Surgery, Roswell Park Cancer Institute, Buffalo, NY 14263.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Takabe
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata City 951-8510, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics*; D005227:Fatty Acids / Q000096:biosynthesis / Q000378:metabolism; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008074:Lipoproteins / Q000096:biosynthesis / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D005227:Fatty Acids; D008074:Lipoproteins; D008246:Lysophospholipids; D018160:Receptors, Cytoplasmic and Nuclear; C060506:sphingosine 1-phosphate; D005947:Glucose; D013110:Sphingosine
keywords: bile duct cancer; fatty acid; liver metabolism; lysosphingolipid; sphingosine kinase