title: Biliary lipid secretion, bile acid metabolism, and gallstone formation are not impaired in hepatic lipase-deficient mice.
abstract: Whereas hepatic lipase (HL) has been implicated in lipoprotein metabolism and atherosclerosis, its role in controlling biliary lipid physiology has not been reported. This work characterizes plasma lipoprotein cholesterol, hepatic cholesterol content, bile acid metabolism, biliary cholesterol secretion, and gallstone formation in HL-deficient mice and C57BL/6 controls fed standard chow, a cholesterol-supplemented diet, or a lithogenic diet. Compared with C57BL/6 controls, HL knockout mice exhibited increased basal plasma high-density lipoprotein (HDL) cholesterol as well as reduced cholesterol levels transported in large lipoproteins in response to cholesterol-enriched diets. Hepatic cholesterol content and biliary cholesterol secretion of chow-fed HL knockout and wild-type mice were not different and increased similarly in both strains after feeding dietary cholesterol or a lithogenic diet. There were no differences in biliary bile acid secretion, bile acid pool size and composition, or fecal bile acid excretion between HL-deficient and control mice. HL knockout mice had a similar prevalence of gallstone formation as compared with control mice when both strains were fed with a lithogenic diet. In conclusion, the deficiency of HL has no major impact on the availability of lipoprotein-derived hepatic cholesterol for biliary secretion; HL expression is not essential for diet-induced gallstone formation in mice.
authors.affiliation: Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Amigo
authors.forename: Pablo
authors.initials: P
authors.lastname: Mardones
authors.forename: Carla
authors.initials: C
authors.lastname: Ferrada
authors.forename: Silvana
authors.initials: S
authors.lastname: Zanlungo
authors.forename: Flavio
authors.initials: F
authors.lastname: Nervi
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Miquel
authors.forename: Attilio
authors.initials: A
authors.lastname: Rigotti
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002769:Cholelithiasis / Q000209:etiology*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D008076:Cholesterol, HDL / Q000097:blood; D004032:Diet / Q000009:adverse effects; D008049:Lipase / Q000172:deficiency*; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008074:Lipoproteins; D002784:Cholesterol; D008049:Lipase