LXR activation and cholesterol efflux from a lipoprotein depot in vivo.
Activation of LXR in cultured cells results in enhancement of cholesterol efflux to apo Al. To study cholesterol efflux, in vivo cationized LDL was injected into the rectus femoris muscle of mice to create a lipoprotein depot. LXR ligand TO901317, 10 mg/kg, was given by gavage for 8 days, starting 4 days after injection of the lipoprotein. The rate of cholesterol efflux from the depot was compared in treated and control mice. Administration of the ligand resulted in a 70% increase in plasma cholesterol and 40% in phospholipids, but HDL-cholesterol and HDL-phospholipids increased by 43% and 24% only. Efflux of the injected cholesterol from the lipoprotein depot of treated mice was not enhanced but even somewhat delayed. This impairment was unexpected and its cause could be multifactorial. A plausible explanation seems that induced hypercholesterolemia, and a decrease in HDL-cholesterol to total cholesterol ratio, delayed the clearance.
Stein
Yechezkiel
Y
Department of Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem 91 120, Israel. ystein@hadassah.org.it
Stein
Olga
O
Dabach
Yedida
Y
Halperin
Gideon
G
Ben-Naim
Mazal
M
D000818:Animals; D000924:Anticholesteremic Agents / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D002788:Cholesterol Esters / Q000737:chemistry / Q000378:metabolism; D008078:Cholesterol, LDL / Q000737:chemistry / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D008074:Lipoproteins / Q000097:blood; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013449:Sulfonamides; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D000924:Anticholesteremic Agents; D002784:Cholesterol; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D008074:Lipoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides