title: Hepatic ABC transporters and triglyceride metabolism.
abstract: OBJECTIVE
  Elevated plasma triglyceride and reduced HDL concentrations are prominent features of metabolic syndrome and type 2 diabetes. Individuals with Tangier disease also have elevated plasma triglyceride concentrations and very low HDL, resulting from mutations in ATP-binding cassette transporter A1 (ABCA1), an integral membrane protein that facilitates nascent HDL particle assembly. Past studies attributed the inverse relationship between plasma HDL and triglyceride to intravascular lipid exchange and catabolic events. However, recent studies also suggest that hepatic signaling and lipid mobilization and secretion may explain how HDL affects plasma triglyceride concentrations.
  
  
  RESULTS
  Hepatocyte-specific ABCA1 knockout mice have markedly reduced plasma HDL and a two-fold increase in triglyceride due to failure to assemble nascent HDL particles by hepatocytes, causing increased catabolism of HDL apolipoprotein A-I and increased hepatic production of triglyceride-enriched VLDL. In-vitro studies suggest that nascent HDL particles may induce signaling to decrease triglyceride secretion. Inhibition of microRNA 33 expression in nonhuman primates augments hepatic ABCA1, genes involved in fatty acid oxidation, and decreases expression of lipogenic genes, causing increased plasma HDL and decreased triglyceride levels.
  
  
  CONCLUSIONS
  New evidence suggests potential mechanisms by which hepatic ABCA1-mediated nascent HDL formation regulates VLDL-triglyceride production and contributes to the inverse relationship between plasma HDL and triglyceride.
authors.affiliation: Departments of Pathology/Section on Lipid Sciences Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina Department of Food Science and Human Nutrition, University of Florida, Gainesville, Florida, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Parks
authors.forename: Soonkyu
authors.initials: S
authors.lastname: Chung
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Shelness
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D014644:Genetic Variation; D006801:Humans; D008099:Liver / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D035683:MicroRNAs; D014280:Triglycerides