Overexpression of SR-BI in hamsters treated with a novel ACAT inhibitor (F12511).
The effect of a novel acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor on cholesterol metabolism was studied in hamsters. Oral administration of F12511 (10 mg/kg/d) for 4 weeks produced a decrease in dietary cholesterol absorption (-18%) and in the liver concentration of esterified cholesterol (-75%), as compared with control values in untreated hamsters. While the hepatic expression of LDLr was unchanged by the treatment, that of SR-BI was increased (+142%), which suggests that the hepatic expression of SR-BI could be upregulated by a depletion of the cholesterol stores, due to ACAT inhibition. This SR-BI overexpression, however, did not induce a fall in plasma HDL-cholesterol concentration, in contrast with previous reports in transgenic mice overexpressing SR-BI at a higher extent.
Milliat
F
F
Laboratoire de physiologie de la nutrition (unité associée à l'Inra), université Paris-Sud, centre d'Orsay, bâtiment 447, 91405 Orsay, France.
Férézou
J
J
Delhon
A
A
Lutton
C
C
D000284:Administration, Oral; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018955:CD36 Antigens / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D002791:Cholesterol, Dietary; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008647:Mesocricetus; D010743:Phospholipids / Q000378:metabolism; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000378:metabolism; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D014280:Triglycerides / Q000378:metabolism
D000813:Anilides; D000924:Anticholesteremic Agents; D018955:CD36 Antigens; D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D010743:Phospholipids; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; C418062:eflucimibe; D002784:Cholesterol; D002785:Sterol O-Acyltransferase