title: Rosiglitazone modifies HDL structure and increases HDL-apo AI synthesis and catabolic rates.
abstract: BACKGROUND
  Rosiglitazone is an agonist of the peroxisome proliferator-activated receptor (PPAR) gamma that may modify HDL metabolism in humans, but this effect has not been completely elucidated. Therefore, we determined the effect of rosiglitazone on apo AI turnover, HDL structure, and PON1 plasma activity.
  
  
  METHODS
  Kinetic studies of HDL-apo AI radiolabeled with (125)I were performed in 7 chow-fed, male, New Zealand white rabbits after 6 weeks of 0.32 mg/kg/d rosiglitazone-treatment vs. vehicle-treated rabbits (n=11). HDL size distribution was determined by polyacrylamide gradient electrophoresis and paraoxonase-1 (PON1); plasma activity was assessed spectrophotometrically using phenylacetate as substrate.
  
  
  RESULTS
  Fractional catabolic rate (FCR) of HDL apo AI was higher in the rosiglitazone-treated group than in the control group (0.031+/-0.004 vs. 0.025+/-0.006 pools/h, respectively, p<0.05). The mean apo AI production rate (PR) was 62% higher in the rosiglitazone group as compared to controls (0.918+/-0.238 vs. 0.564+/-0.160 mg/kg/h, p<0.01). Accordingly, apo AI plasma levels in rosiglitazone-treated animals were about 37% higher than in the control group. Rosiglitazone-induced changes in apo AI turnover appeared concomitantly with a significant increase of phospholipids and a decrease in colesteryl esters content of the HDL. Compositional changes resulted in a relative increase of the HDL3b and HDL3c subfractions and a significant enhancement of the plasma PON1 activity (488.5+/-138.2 vs. 595.2+/-179.4 micromol/min/ml, p<0.05).
  
  
  CONCLUSIONS
  Rosiglitazone increased apo AI plasma concentrations, resulting from an enhancement of apo AI synthesis, and induced the synthesis of smaller HDL particles with a concomitant increase of plasma PON1 activity. These modifications may contribute to the anti-atherogenic potential of rosiglitazone.
authors.affiliation: Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Carreón-Torres
authors.forename: Karla
authors.initials: K
authors.lastname: Rendón-Sauer
authors.forename: Mariana
authors.initials: M
authors.lastname: Monter-Garrido
authors.forename: Paola
authors.initials: P
authors.lastname: Toledo-Ibelles
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gamboa
authors.forename: Marta
authors.initials: M
authors.lastname: Menjivar
authors.forename: Rebeca
authors.initials: R
authors.lastname: López-Marure
authors.forename: Gerald
authors.initials: G
authors.lastname: Luc
authors.forename: Catherine
authors.initials: C
authors.lastname: Fievet
authors.forename: David
authors.initials: D
authors.lastname: Cruz
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vargas-Alarcón
authors.forename: Oscar
authors.initials: O
authors.lastname: Pérez-Méndez
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D043303:Aryldialkylphosphatase / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D008076:Cholesterol, HDL / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D047495:PPAR gamma / Q000819:agonists; D011817:Rabbits; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D001786:Blood Glucose; D008076:Cholesterol, HDL; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human