title: Novel Pathways of Apolipoprotein A-I Metabolism in High-Density Lipoprotein of Different Sizes in Humans.
abstract: OBJECTIVE
  A prevailing concept is that high-density lipoprotein (HDL) is secreted into the systemic circulation as a small mainly discoidal particle, which expands progressively and becomes spherical by uptake and esterification of cellular cholesterol and then contracts by cholesterol ester delivery to the liver, a process known as reverse cholesterol transport, thought to be impaired in people with low HDL cholesterol (HDLc). This metabolic framework has not been established in humans.
  
  
  RESULTS
  We studied the metabolism of apolipoprotein A-I in 4 standard HDL sizes by endogenous isotopic labeling in 6 overweight adults with low HDLc and in 6 adults with normal body weight with high plasma HDLc. Contrary to expectation, HDL was secreted into the circulation in its entire size distribution from very small to very large similarly in both groups. Very small (prebeta) HDL comprised only 8% of total apolipoprotein A-I secretion. Each HDL subfraction circulated mostly within its secreted size range for 1 to 4 days and then was cleared. Enlargement of very small and medium to large and very large HDL and generation of very small from medium HDL were minor metabolic pathways. Prebeta HDL was cleared slower, whereas medium, large, and very large HDL were cleared faster in the low HDLc group.
  
  
  CONCLUSIONS
  A new model is proposed from these results in which HDL is metabolized in plasma mainly within several discrete, stable sizes across the common range of HDLc concentrations.
authors.affiliation: From the School of Medicine, Universidad de los Andes, Bogotá, Colombia (C.O.M.); Section of Endocrinology, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia (C.O.M.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (C.O.M., J.F., A.M.M., L.W., F.M.S.); and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (F.M.S.).
authors.forename: Carlos O
authors.initials: CO
authors.lastname: Mendivil
authors.affiliation: From the School of Medicine, Universidad de los Andes, Bogotá, Colombia (C.O.M.); Section of Endocrinology, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia (C.O.M.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (C.O.M., J.F., A.M.M., L.W., F.M.S.); and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (F.M.S.).
authors.forename: Jeremy
authors.initials: J
authors.lastname: Furtado
authors.affiliation: From the School of Medicine, Universidad de los Andes, Bogotá, Colombia (C.O.M.); Section of Endocrinology, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia (C.O.M.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (C.O.M., J.F., A.M.M., L.W., F.M.S.); and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (F.M.S.).
authors.forename: Allyson M
authors.initials: AM
authors.lastname: Morton
authors.affiliation: From the School of Medicine, Universidad de los Andes, Bogotá, Colombia (C.O.M.); Section of Endocrinology, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia (C.O.M.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (C.O.M., J.F., A.M.M., L.W., F.M.S.); and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (F.M.S.).
authors.forename: Liyun
authors.initials: L
authors.lastname: Wang
authors.affiliation: From the School of Medicine, Universidad de los Andes, Bogotá, Colombia (C.O.M.); Section of Endocrinology, Hospital Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia (C.O.M.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (C.O.M., J.F., A.M.M., L.W., F.M.S.); and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (F.M.S.). fsacks@hsph.harvard.edu.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sacks
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D053442:High-Density Lipoproteins, Pre-beta / Q000097:blood; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D050177:Overweight / Q000097:blood*; D010316:Particle Size
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D015415:Biomarkers; D008076:Cholesterol, HDL; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL
keywords: apolipoprotein; cholesterol; high-density lipoprotein; liver; metabolism