title: Myristic acid is associated to low plasma HDL cholesterol levels in a Mediterranean population and increases HDL catabolism by enhancing HDL particles trapping to cell surface proteoglycans in a liver hepatoma cell model.
abstract: BACKGROUND
  HDL-C plasma levels are modulated by dietary fatty acid (FA), but studies investigating dietary supplementation in FA gave contrasting results. Saturated FA increased HDL-C levels only in some studies. Mono-unsaturated FA exerted a slight effect while poly-unsaturated FA mostly increased plasma HDL-C.
  
  
  OBJECTIVE
  This study presents two aims: i) to investigate the relationship between HDL-C levels and plasma FA composition in a Sicilian population following a "Mediterranean diet", ii) to investigate if FA that resulted correlated with plasma HDL-C levels in the population study and/or very abundant in the plasma were able to affect HDL catabolism in an "in vitro" model of cultured hepatoma cells (HepG2).
  
  
  RESULTS
  plasma HDL-C levels in the population correlated negatively with myristic acid (C14:0, β = -0.24, p < 0.01), oleic acid (C18:1n9, β = -0.22, p < 0.01) and cis-11-Eicosenoic (C20:1n9, β = -0.19, p = 0.01) and positively with palmitoleic acid (C16:1, β = +0.19, p = 0.03). HepG2 cells were conditioned with FA before evaluating HDL binding kinetics, and only C14:0 increased HDL binding by a non-saturable pathway. After removal of heparan sulphate proteoglycans (HSPG) by heparinases HDL binding dropped by 29% only in C14:0 conditioned cells (p < 0.05). C14:0 showed also the highest internalization of HDL-derived cholesteryl esters (CE, +32% p = 0.01 vs. non-conditioned cells).
  
  
  CONCLUSIONS
  C14:0 was correlated with decreased plasma HDL-C levels in a Mediterranean population. C14:0 might reduce HDL-C levels by increasing HDL trapping to cell surface HSPG and CE stripping from bound HDL. Other mechanisms are to be investigated to explain the effects of other FA on HDL metabolism.
authors.affiliation: Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Noto
authors.affiliation: Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fayer
authors.affiliation: Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Angelo B
authors.initials: AB
authors.lastname: Cefalù
authors.affiliation: Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Altieri
authors.affiliation: Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Palesano
authors.affiliation: Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Spina
authors.affiliation: Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Valenti
authors.affiliation: Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Pitrone
authors.affiliation: Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pizzolanti
authors.affiliation: Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Barbagallo
authors.affiliation: Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Giordano
authors.affiliation: Department of Biomedicine, Internal Medicine and Medical Specialties (DIBIMIS), University of Palermo, Palermo, Italy. Electronic address: avernam@mbox.unipa.it.
authors.forename: Maurizio R
authors.initials: MR
authors.lastname: Averna
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D038441:Diet, Mediterranean; D005260:Female; D056945:Hep G2 Cells; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D019814:Myristic Acid / Q000097:blood*; D011485:Protein Binding; D012802:Sicily
chemical_list: D015415:Biomarkers; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D019812:Heparan Sulfate Proteoglycans; D008565:Membrane Proteins; D019814:Myristic Acid
keywords: Fatty acids; HDL cholesterol levels; HepG2 cells; Population study