Impact of android overweight or obesity and insulin resistance on basal and postprandial SR-BI and ABCA1-mediated serum cholesterol efflux capacities.
Since android overweight/obesity and insulin resistance are independent risk factors for cardiovascular disease, we investigated their impact on basal and postprandial scavenger receptor BI (SR-BI) and ATP binding cassette transporter A1 (ABCA1)-mediated serum cholesterol efflux. Twelve android overweight to obese and 9 normal weight controls women underwent body composition analysis by dual energy X-ray absorptiometry, a euglycemic hyperinsulinemic clamp, and an oral fat load with blood sampling at initial time (T0), 4h (T4) and 10h (T10) after the fat load. Serum lipids and HDL-parameters, capacities of serum to promote cholesterol efflux from SR-BI expressing Fu5AH hepatoma cells or from ABCA1-expressing J774 macrophages and to abilities of serum to induce a net removal of cholesterol from macrophage foam cells were measured at T0, T4 and T10. Sera from overweight/obese exhibited moderately decreased SR-BI-mediated cholesterol efflux capacities, in accordance with reduced HDL concentrations, but importantly increased ABCA1-mediated cholesterol efflux and increased cholesterol extraction capacities over the postprandial period, partly related to higher prebeta-HDL concentrations. In multiple regression analyses, android obesity-related parameters and HDL-PL or prebeta-HDL levels remained the only independent correlates for SR-BI or ABCA1-dependent fractional cholesterol efflux while only prebeta-HDL levels remained correlated to cholesterol extraction capacities. Our results suggest that android overweight/obesity may not result in an impaired cholesterol efflux capacity.
Attia
Nesrine
N
Univ Paris-Sud, UMR INRA 1154, UFR de Pharmacie, 5 rue JB Clément, 92296 Châtenay-Malabry, France.
Fournier
Natalie
N
Vedie
Benoît
B
Cambillau
Michèle
M
Beaune
Philippe
P
Ziegler
Olivier
O
Grynberg
Alain
A
Paul
Jean-Louis
JL
Guerci
Bruno
B
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000097:blood*; D000328:Adult; D000818:Animals; D001823:Body Composition; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000097:blood*; D005260:Female; D005487:Foam Cells / Q000378:metabolism; D053442:High-Density Lipoproteins, Pre-beta / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008113:Liver Neoplasms / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D050177:Overweight / Q000097:blood*; D019518:Postprandial Period; D051381:Rats; D051122:Scavenger Receptors, Class B / Q000097:blood*; D014407:Tumor Cells, Cultured; D055105:Waist Circumference
C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D053442:High-Density Lipoproteins, Pre-beta; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D002784:Cholesterol