Print Email Facebook Twitter Increased fecal bile acid excretion in transgenic mice with elevated expression of human phospholipid transfer protein Title Increased fecal bile acid excretion in transgenic mice with elevated expression of human phospholipid transfer protein Author Post, S.M. de Crom, R. van Haperen, R. van Tol, A. Princen, H.M.G. Gaubius Instituut TNO Publication year 2003 Abstract Objective - HDL plays a key role in protection against development of atherosclerosis by promoting reverse cholesterol transport from peripheral tissues to the liver for secretion into bile. Phospholipid transfer protein (PLTP) promotes the transfer of phospholipids between lipoproteins and modulates HDL size and composition, thereby having a crucial role in HDL metabolism. We investigated the effect of increased PLTP activity on removal of cholesterol from the body. Methods and Results - On a chow diet, transgenic mice overexpressing human PLTP have a 15-fold increased plasma PLTP activity compared with wild-type mice (572.4±59.2 versus 38.6±3.6 μmol/mL per h). Plasma cholesterol, mainly present in HDL, is strongly decreased (-92%), caused by a rapid clearance from the circulation by the liver and leading to a 1.8-fold increase in hepatic cholesteryl esters. This results in a 2-fold increase in biliary bile acid secretion without changing the bile saturation index. Consequently, the transgenic mice show a 1.4-fold increase in the amount of excreted fecal bile acids compared with wild-type mice, whereas fecal neutral sterol excretion is unchanged. Conclusions - Our data show that elevation of PLTP activity results in rapid disposal of cholesterol from the body via increased conversion into bile acids and subsequent excretion. Chemicals/CAS: Bile Acids and Salts; Carrier Proteins; Cholesterol, 57-88-5; Cholesterol, HDL; Lipase, EC 22.214.171.124; Lipoprotein Lipase, EC 126.96.36.199; Membrane Proteins; Phospholipid Transfer Proteins; Sterols Subject BiologyBiomedical ResearchBile acidHDLMousePhospholipid transfer proteinReverse cholesterol transportAnimalsBile Acids and SaltsBiological TransportCarrier ProteinsCholesterolCholesterol, HDLFecesHumansLipaseLipoprotein LipaseLiverMaleMembrane ProteinsMiceMice, Inbred C57BLMice, TransgenicPhospholipid Transfer ProteinsSterols To reference this document use: http://resolver.tudelft.nl/uuid:2adac067-76bf-4a9e-8c75-0ec3953327d5 DOI https://doi.org/10.1161/01.atv.0000067702.22390.20 TNO identifier 237071 ISSN 1079-5642 Source Arteriosclerosis, Thrombosis, and Vascular Biology, 23 (5), 892-897 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.