title: Ablating L-FABP in SCP-2/SCP-x null mice impairs bile acid metabolism and biliary HDL-cholesterol secretion.
abstract: On the basis of their abilities to bind bile acids and/or cholesterol, the physiological role(s) of liver fatty acid-binding protein (L-FABP) and sterol carrier protein (SCP) 2/SCP-x (SCP-2/SCP-x) gene products in biliary bile acid and cholesterol formation was examined in gene-ablated male mice. L-FABP (LKO) or L-FABP/SCP-2/SCP-x [triple-knockout (TKO)] ablation markedly decreased hepatic bile acid concentration, while SCP-2/SCP-x [double-knockout (DKO)] ablation alone had no effect. In contrast, LKO increased biliary bile acid, while DKO and TKO had no effect on biliary bile acid levels. LKO and DKO also altered biliary bile acid composition to increase bile acid hydrophobicity. Furthermore, LKO and TKO decreased hepatic uptake and biliary secretion of high-density lipoprotein (HDL)-derived 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol), while DKO alone had no effect. Finally, LKO and, to a lesser extent, DKO decreased most indexes contributing to cholesterol solubility in biliary bile. These results suggest different, but complementary, roles for L-FABP and SCP-2/SCP-x in biliary bile acid and cholesterol formation. L-FABP appears to function more in hepatic retention of bile acids as well as hepatic uptake and biliary secretion of HDL-cholesterol. Conversely, SCP-2/SCP-x may function more in formation and biliary secretion of bile acid, with less impact on hepatic uptake or biliary secretion of HDL-cholesterol.
authors.affiliation: Department of Physiology and Pharmacology, Texas A & M University, College Station, Texas;
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Martin
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan;
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Atshaves
authors.affiliation: Department of Pathobiology, Texas A & M University, College Station, Texas; and.
authors.forename: Kerstin K
authors.initials: KK
authors.lastname: Landrock
authors.affiliation: Department of Pathobiology, Texas A & M University, College Station, Texas; and.
authors.forename: Danilo
authors.initials: D
authors.lastname: Landrock
authors.affiliation: Department of Physiology and Pharmacology, Texas A & M University, College Station, Texas;
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Storey
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Howles
authors.affiliation: Department of Pathobiology, Texas A & M University, College Station, Texas; and.
authors.forename: Ann B
authors.initials: AB
authors.lastname: Kier
authors.affiliation: Department of Physiology and Pharmacology, Texas A & M University, College Station, Texas; fschroeder@cvm.tamu.edu.
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Schroeder
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010743:Phospholipids / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D002352:Carrier Proteins; D008076:Cholesterol, HDL; C493320:Fabp1 protein, mouse; D050556:Fatty Acid-Binding Proteins; D010743:Phospholipids; C072087:sterol carrier proteins; D002784:Cholesterol
keywords: bile acid; cholesterol; fatty acid-binding protein; gene ablation; mouse