title: Basal and postprandial serum-promoted cholesterol efflux in normolipidemic subjects: Importance of fat mass distribution.
abstract: Excess of adipose tissue may affect the reverse cholesterol transport mediated by high-density lipoprotein (HDL). Impairments in this system may be one possible factor favoring atherosclerosis development in obesity. To investigate if gender and regional fat mass distribution independently influence reverse cholesterol transport (RCT), we studied in vitro the capacity of serum to promote the cell cholesterol efflux. Measurements were performed both in the fasting state and in the postprandial state, a setting known to stimulate cholesterol transport and altered in obesity. Thirteen obese women with an android phenotype, waist-to-hip ratio (WHR): 0.98 to 0.85 and 51 normal-weight subjects: 25 women and 26 men, with a similar WHR range: 0.96 to 0.67, were recruited. All the participants were normolipoproteinemic in the fasting state and were given an oral fat load. Blood samples were taken before giving the oral fat load and after every 2 hours. The measurements of the ability of serum to promote cholesterol efflux from cells were performed using 3H-cholesterol labeled Fu5AH hepatoma cells in the fasting state 6 and 8 hours after the lipid rich meal. Incremental serum triglyceride (TG), area under the curve (iAUC) and AUC of retinyl palmitate (RP) for the obese women and nonobese subjects were similar. Basal cholesterol efflux was reduced in obese women compared with normal-weight women (26.75% +/- 3.1% v 30.81% +/- 4.2%, P =.004). However, the magnitude of cholesterol efflux promoted by whole serum increased similarly in all the groups. In the subjects with similar WHR, no gender difference was observed in the postprandial TG response and in the first step of RCT. Multivariate regression analyses indicated that plasma HDL-cholesterol (HDL-C) concentration is the best predictor of cholesterol efflux in the fasting state with an independent mild additive effect of WHR. Conversely, postprandial efflux appeared to be mostly related to the WHR with a mild additive effect of HDL-C. Our results indicate that alterations in the first step of RCT can occur in normolipidemic obese subjects and are tightly associated with the abdominal distribution of fat mass. Android obesity in women brings them to the level of men with respect to RCT.
authors.affiliation: Laboratoire de la Fédération d'endocrinologie, diabétologie et maladies de la nutrition, Hôpital de l'Antiquaille, Lyon, France.
authors.forename: D
authors.initials: D
authors.lastname: Autran
authors.forename: B
authors.initials: B
authors.lastname: Guerci
authors.forename: J L
authors.initials: JL
authors.lastname: Paul
authors.forename: P
authors.initials: P
authors.lastname: Moulin
authors.forename: B
authors.initials: B
authors.lastname: Vergés
authors.forename: V
authors.initials: V
authors.lastname: Durlach
authors.forename: A
authors.initials: A
authors.lastname: Girard-Globa
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001681:Biological Assay; D001798:Blood Proteins / Q000494:pharmacology*; D001823:Body Composition / Q000502:physiology*; D001824:Body Constitution; D015992:Body Mass Index; D001835:Body Weight; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D005215:Fasting / Q000097:blood; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood*; D019518:Postprandial Period / Q000502:physiology; D012016:Reference Values; D012737:Sex Factors; D014407:Tumor Cells, Cultured
chemical_list: D001798:Blood Proteins; D017077:Culture Media, Conditioned; D004041:Dietary Fats; D008055:Lipids; D002784:Cholesterol