title: Liver-specific phospholipid transfer protein deficiency reduces high-density lipoprotein and non-high-density lipoprotein production in mice.
abstract: OBJECTIVE
  The liver is one of the critical organs for lipoprotein metabolism and a major source for phospholipid transfer protein (PLTP) expression. The effect of liver-specific PLTP deficiency on plasma lipoprotein production and metabolism in mice was investigated.
  
  
  RESULTS
  We created a liver-specific PLTP-deficient mouse model. We measured plasma high-density lipoprotein (HDL) and apolipoprotein B (apoB)-containing lipoprotein (or non-HDL) levels and their production rates. We found that hepatic ablation of PLTP leads to a significant decrease in plasma PLTP activity, HDL lipids, non-HDL lipids, apoAI, and apoB levels. In addition, nuclear magnetic resonance examination of lipoproteins showed that the deficiency decreases HDL and apoB-containing lipoprotein particle numbers, as well as very low-density lipoprotein particle size, which was confirmed by electron microscopy. Moreover, HDL particles from the deficient mice are lipid-poor ones. To unravel the mechanism, we evaluated the apoB and triglyceride production rates. We found that hepatic PLTP deficiency significantly decreases apoB and triglyceride secretion rates. To investigate the role of liver PLTP on HDL production, we set up primary hepatocyte culture studies and found that the PLTP-deficient hepatocytes produce less nascent HDL. Furthermore, we found that exogenous PLTP promotes nascent HDL production through an ATP-binding cassette A 1-mediated pathway.
  
  
  CONCLUSIONS
  Liver-specific PLTP deficiency significantly reduces plasma HDL and apoB-containing lipoprotein levels. Reduction of production rates of both particles is one of the mechanisms.
authors.affiliation: Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
authors.forename: Amirfarbod
authors.initials: A
authors.lastname: Yazdanyar
authors.forename: Wei
authors.initials: W
authors.lastname: Quan
authors.forename: Weijun
authors.initials: W
authors.lastname: Jin
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Jiang
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D015536:Down-Regulation; D022781:Hepatocytes / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D049294:Phospholipid Transfer Proteins / Q000172:deficiency* / Q000235:genetics; D061251:Primary Cell Culture; D014280:Triglycerides / Q000097:blood
chemical_list: C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D015415:Biomarkers; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; D049294:Phospholipid Transfer Proteins; D014280:Triglycerides; C510091:phospholipid transfer protein, mouse
keywords: atherosclerosis; high-density lipoproteins; liver; phospholipid transfer protein; very low-density lipoproteins