title: Relative contributions of L-FABP, SCP-2/SCP-x, or both to hepatic biliary phenotype of female mice.
abstract: Both sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x) and liver fatty acid binding protein (L-FABP) have been proposed to function in hepatobiliary bile acid metabolism/accumulation. To begin to address this issue, the impact of ablating L-FABP (LKO) or SCP-2/SCP-x (DKO) individually or both together (TKO) was examined in female mice. Biliary bile acid levels were decreased in LKO, DKO, and TKO mice; however, hepatic bile acid concentration was decreased in LKO mice only. In contrast, biliary phospholipid level was decreased only in TKO mice, while biliary cholesterol levels were unaltered regardless of phenotype. The loss of either or both genes increased hepatic expression of the major bile acid synthetic enzymes (CYP7A1 and/or CYP27A1). Loss of L-FABP and/or SCP-2/SCP-x genes significantly altered the molecular composition of biliary bile acids, but not the proportion of conjugated/unconjugated bile acids or overall bile acid hydrophobicity index. These data suggested that L-FABP was more important in hepatic retention of bile acids, while SCP-2/SCP-x more broadly affected biliary bile acid and phospholipid levels.
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, USA.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Martin
authors.affiliation: Department of Pathobiology, Texas A&M University, College Station, TX 77843-4467, USA.
authors.forename: Danilo
authors.initials: D
authors.lastname: Landrock
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, USA.
authors.forename: Kerstin K
authors.initials: KK
authors.lastname: Landrock
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45219, USA.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Howles
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Atshaves
authors.affiliation: Department of Pathobiology, Texas A&M University, College Station, TX 77843-4467, USA.
authors.forename: Ann B
authors.initials: AB
authors.lastname: Kier
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, USA. Electronic address: fschroeder@cvm.tamu.edu.
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Schroeder
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism; D001659:Biliary Tract / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D010743:Phospholipids / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D002352:Carrier Proteins; C493320:Fabp1 protein, mouse; D050556:Fatty Acid-Binding Proteins; D010743:Phospholipids; C072087:sterol carrier proteins; D002784:Cholesterol
keywords: Bile acid; Gene ablation; L-FABP; SCP-2; SCP-x; Sexual dimorphism