title: The effects of apolipoprotein F deficiency on high density lipoprotein cholesterol metabolism in mice.
abstract: Apolipoprotein F (apoF) is 29 kilodalton secreted sialoglycoprotein that resides on the HDL and LDL fractions of human plasma. Human ApoF is also known as Lipid Transfer Inhibitor protein (LTIP) based on its ability to inhibit cholesteryl ester transfer protein (CETP)-mediated transfer events between lipoproteins. In contrast to other apolipoproteins, ApoF is predicted to lack strong amphipathic alpha helices and its true physiological function remains unknown. We previously showed that overexpression of Apolipoprotein F in mice reduced HDL cholesterol levels by 20-25% by accelerating clearance from the circulation. In order to investigate the effect of physiological levels of ApoF expression on HDL cholesterol metabolism, we generated ApoF deficient mice. Unexpectedly, deletion of ApoF had no substantial impact on plasma lipid concentrations, HDL size, lipid or protein composition. Sex-specific differences were observed in hepatic cholesterol content as well as serum cholesterol efflux capacity. Female ApoF KO mice had increased liver cholesteryl ester content relative to wild type controls on a chow diet (KO: 3.4+/-0.9 mg/dl vs. WT: 1.2+/-0.3 mg/dl, p<0.05). No differences were observed in ABCG1-mediated cholesterol efflux capacity in either sex. Interestingly, ApoB-depleted serum from male KO mice was less effective at promoting ABCA1-mediated cholesterol efflux from J774 macrophages relative to WT controls.
authors.affiliation: Division of Translational Medicine and Human Genetics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America. wlagor@mail.med.upenn.edu
authors.forename: William R
authors.initials: WR
authors.lastname: Lagor
authors.forename: David W
authors.initials: DW
authors.lastname: Fields
authors.forename: Sumeet A
authors.initials: SA
authors.lastname: Khetarpal
authors.forename: Arthi
authors.initials: A
authors.lastname: Kumaravel
authors.forename: Wen
authors.initials: W
authors.lastname: Lin
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Weintraub
authors.forename: Kaijin
authors.initials: K
authors.lastname: Wu
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Hamm-Alvarez
authors.forename: Denise
authors.initials: D
authors.lastname: Drazul-Schrader
authors.forename: Margarita
authors.initials: M
authors.lastname: de la Llera-Moya
authors.forename: George H
authors.initials: GH
authors.lastname: Rothblat
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000172:deficiency* / Q000378:metabolism; D001692:Biological Transport; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D059305:Diet, High-Fat; D005247:Feeding Behavior; D005260:Female; D017930:Genes, Reporter; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D013194:Staining and Labeling; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001053:Apolipoproteins; D008076:Cholesterol, HDL; C036321:apolipoprotein F; D001616:beta-Galactosidase